BASIC RESEARCH
EXPERIMENTAL MODELS OF HEPATECTOMY AND LIVER REGENERATION USING NEWBORN AND WEANING RATS
Ana Cristina Aoun Tannuri, Uenis Tannuri, Maria Cecília Coelho, Neide Aparecida dos Santos, Evandro Sobroza de Mello
Pediatric Surgery Laboratory (LIM 30) and Liver Function Research Laboratory (LIM-14), Faculdade de Medicina, Universidade de São Paulo/SP, Brazil
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Results of statistical analyses of differences among groups at the end of the study (Day 110) are shown below the respective panels.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ana Lúcia Mattar, Flávia Gomes Machado, Clarice Kazue Fujihara, Denise Maria Avancini Costa Malheiros, Roberto Zatz" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Ana Lúcia" "apellidos" => "Mattar" ] 1 => array:2 [ "nombre" => "Flávia Gomes" "apellidos" => "Machado" ] 2 => array:2 [ "nombre" => "Clarice Kazue" "apellidos" => "Fujihara" ] 3 => array:2 [ "nombre" => "Denise Maria Avancini Costa" "apellidos" => "Malheiros" ] 4 => array:2 [ "nombre" => "Roberto" "apellidos" => "Zatz" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222028745?idApp=UINPBA00004N" "url" => "/18075932/0000006200000006/v1_202212060917/S1807593222028745/v1_202212060917/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">BASIC RESEARCH</span>" "titulo" => "EXPERIMENTAL MODELS OF HEPATECTOMY AND LIVER REGENERATION USING NEWBORN AND WEANING RATS" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "757" "paginaFinal" => "762" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Ana Cristina Aoun Tannuri, Uenis Tannuri, Maria Cecília Coelho, Neide Aparecida dos Santos, Evandro Sobroza de Mello" "autores" => array:5 [ 0 => array:3 [ "nombre" => "Ana Cristina Aoun" "apellidos" => "Tannuri" "email" => array:1 [ 0 => "cristannuri@uol.com.br" ] ] 1 => array:2 [ "nombre" => "Uenis" "apellidos" => "Tannuri" ] 2 => array:2 [ "nombre" => "Maria Cecília" "apellidos" => "Coelho" ] 3 => array:2 [ "nombre" => "Neide Aparecida" "apellidos" => "dos Santos" ] 4 => array:2 [ "nombre" => "Evandro Sobroza" "apellidos" => "de Mello" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Pediatric Surgery Laboratory (LIM 30) and Liver Function Research Laboratory (LIM-14), Faculdade de Medicina, Universidade de São Paulo/SP, Brazil" "identificador" => "aff1" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig8" "etiqueta" => "Figure 8" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr8.jpeg" "Alto" => 784 "Ancho" => 994 "Tamanyo" => 209163 ] ] "descripcion" => array:1 [ "en" => "<p id="spara80" class="elsevierStyleSimplePara elsevierViewall">Photomicrograph of a weaning rat liver on the first day after PH, with an apoptotic body. See eosinophilic cytoplasm and dense nuclear fragments arrow (original magnification X 1500, under oil immersion).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle110">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">The liver has significant regenerative capacity after injury. Even after major insult, such as extensive surgical resection, its function usually recovers within a couple of weeks. This is accomplished through complex mechanisms that have not been fully elucidated.<a class="elsevierStyleCrossRef" href="#bib1"><span class="elsevierStyleSup">1</span></a></p><p id="para20" class="elsevierStylePara elsevierViewall">Studies of liver regeneration in humans are difficult because of the heterogeneous etiology of liver lesions that precede regeneration.<a class="elsevierStyleCrossRef" href="#bib2"><span class="elsevierStyleSup">2</span></a> For these reasons, investigation of liver regeneration in standardized experimental models seems to be more useful than clinical studies. Regeneration models may be <span class="elsevierStyleItalic">in vitro</span> and <span class="elsevierStyleItalic">in vivo.</span> Cultured hepatocytes (<span class="elsevierStyleItalic">in vitro</span> model) have very different physiological responses relative to <span class="elsevierStyleItalic">in vivo</span> models, and it has been increasingly recognized that non-parenchymal cells may play an important role in <span class="elsevierStyleItalic">in vivo</span> regeneration because their interaction with hepatocytes is implicated in all physiological responses of the liver.<a class="elsevierStyleCrossRef" href="#bib3"><span class="elsevierStyleSup">3</span></a></p><p id="para30" class="elsevierStylePara elsevierViewall">In 1931, Higgins and Anderson published a model of 70% hepatectomy in adult rats<a class="elsevierStyleCrossRef" href="#bib4"><span class="elsevierStyleSup">4</span></a>, which has been employed heavily in investigations of hepatic regeneration.<a class="elsevierStyleCrossRefs" href="#bib5"><span class="elsevierStyleSup">5,6</span></a> Small animals, such as mice and rats, are useful because they are easy to manage and represent minimal logistical, financial or ethical problems<a class="elsevierStyleCrossRef" href="#bib2"><span class="elsevierStyleSup">2</span></a>. However, physiological differences, such as having a faster metabolism relative to humans, must be considered. Under normal circumstances, the human liver initiates regeneration within 3 days and reaches its original size by 3-6 months.<a class="elsevierStyleCrossRef" href="#bib1"><span class="elsevierStyleSup">1</span></a> In rats, the interval between partial hepatectomy and initiation of DNA synthesis in hepatocytes is 10 to 12 hours and peaks at about 24 hours.<a class="elsevierStyleCrossRef" href="#bib7"><span class="elsevierStyleSup">7</span></a> Liver weight is completely recovered by the seventh day. Histological examination reveals slight hypertrophy of both cytoplasmic bodies and nuclei. Mitosis begins by the end of the first day, and cell division is completed on the second and third days.<a class="elsevierStyleCrossRef" href="#bib4"><span class="elsevierStyleSup">4</span></a></p><p id="para40" class="elsevierStylePara elsevierViewall">In normal individuals, liver regeneration can be affected by a number of factors that jeopardize the quality and end result of the process. Aging is one of these factors. Biondo-Simões et al. observed that hepatocyte replication is delayed in the livers of older animals.<a class="elsevierStyleCrossRef" href="#bib8"><span class="elsevierStyleSup">8</span></a> Therefore, the phenomena involved in the liver regeneration of developing animals are characterized by different intensity and quality, as compared to the adult animals.</p><p id="para50" class="elsevierStylePara elsevierViewall">Understanding hepatic regeneration in children has become more important lately due to partial liver transplantations that have been performed with increasing frequency in this age group of patients.<a class="elsevierStyleCrossRefs" href="#bib9"><span class="elsevierStyleSup">9–11</span></a> Although the Higgins and Anderson model has been used extensively, there are no studies of hepatectomy and liver regeneration in growing animal models.</p><p id="para60" class="elsevierStylePara elsevierViewall">The aims of the present experimental study were: 1) to standardize two animal models of partial hepatectomy (PH) and liver regeneration using newborn suckling and weaning rats, and 2) to study the evolution of remnant liver weight and histological changes of regenerating hepatic parenchyma on the days following partial hepatectomy.</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle120">MATERIAL AND METHODS</span><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle130">Animals</span><p id="para70" class="elsevierStylePara elsevierViewall">Fifty newborn suckling rats (age 5-7 days, weight 6-10 g) and forty-four weaning rats (age 21-23 days, weight 30-50 g) were operated upon. All animals received care according to the criteria outlined in the “Guide for Care and Use of Laboratory Animals” prepared by the National Academy of Sciences; this study protocol and the anesthetic procedures were approved by the Animal Ethic Committee of University of São Paulo Medical School.</p><p id="para80" class="elsevierStylePara elsevierViewall">The suckling rats were maintained with their mothers in stainless steel cages. The weaning rats were kept on standard laboratory diet and tap water <span class="elsevierStyleItalic">ad libitum</span> throughout the experiment.</p></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle140">Creation of experimental models</span><p id="para90" class="elsevierStylePara elsevierViewall">All the animals were operated on by the same two surgeons (UT and ACAT) wearing surgical telescopes (magnification 3.5X) and microsurgical instruments. The surgical procedures were performed under sterile conditions between 9:00 AM and 10:00 AM, due to the circadian rhythm of liver regeneration. Ether-soaked gauze was kept near the animals’ nose to induce and maintain anesthesia. This type of anesthesia is considered safe for small animals subjected to short surgical procedures. Following a 1cm midline incision, the upper abdomen and lateral lower portions of both hemi-thoraces were compressed to exteriorize the liver. Consequently, adequate mobilization and exposure of the liver could be attained without dividing the ligaments of the right and left lobes (<a class="elsevierStyleCrossRef" href="#fig1">Fig. 1</a>). The liver parenchyma could not be touched because of the dangers of injuring the viscera and bleeding. A 2-0 cotton thread knot, surrounding the hilum and also the hepatic vein, was tied and the right medial, left medial and left lateral lobes were resected <span class="elsevierStyleItalic">en bloc</span> (<a class="elsevierStyleCrossRefs" href="#fig2">Fig. 2 and 3</a>). Because the rat liver is lobulated, the hilum of these lobes could be safely ligated without involving the vasculature of the remnant lobes. The abdomen was closed with a single-layer running suture using 6-0 prolene. Following surgery, the suckling animals were returned to their mothers, and the weaning animals were fed regular diets and water <span class="elsevierStyleItalic">ad libitum.</span> The animals were sacrificed 0 (just after the hepatectomy), 1, 2, 3, 4 or 7 days after the operation, under ether anesthesia, and the body weights were determined. A midline single abdominal and thoracic incision was performed to harvest the remnant liver lobes, which were then weighed and fixed in 10% neutral buffered formalin for routine histology. Groups of normal non-operated weaning and suckling animals served as controls.</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><elsevierMultimedia ident="fig2"></elsevierMultimedia><elsevierMultimedia ident="fig3"></elsevierMultimedia></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle150">Histological analysis</span><p id="para100" class="elsevierStylePara elsevierViewall">Qualitative histological examination was performed in 4-µm thick sections of all liver samples (x 300, 600 and 1500). Lobular architecture, as well as presence of mitotic figures, apoptotic bodies and steatosis, was evaluated.</p></span><span id="cesec60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle160">Statistical analysis</span><p id="para110" class="elsevierStylePara elsevierViewall">The mortality rates of the groups were expressed as percentages and were compared using the Fisher test. The other results were expressed as means ± SD. For statistical purposes, ANOVA and Bonferroni tests were employed (liver weights/body weight ratios presented a parametric distribution). Ρ < 0.05 was considered significant.</p></span></span><span id="cesec70" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle170">RESULTS</span><span id="cesec80" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle180">Mortality rates</span><p id="para120" class="elsevierStylePara elsevierViewall">Twelve deaths occurred in the newborn group (24%). The causes were anesthetic complications, cut surface bleeding and maternal cannibalism. There were no deaths in the weaning group. The comparison of mortality rates of groups demonstrated a significant difference (P = 0.003).</p></span><span id="cesec90" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle190">Liver weight/body weight ratios following partial hepatectomy</span><p id="para130" class="elsevierStylePara elsevierViewall">To evaluate growth of the remnant liver following PH, the liver weight/body weight ratio was calculated on 0, 1, 2, 3, 4 and 7 days after hepatectomy (<a class="elsevierStyleCrossRef" href="#fig4">Fig. 4</a>).</p><elsevierMultimedia ident="fig4"></elsevierMultimedia><p id="para140" class="elsevierStylePara elsevierViewall">There was a significant decrease in liver mass just after PH (P < 0.0001 for both newborn and weaning groups). On the seventh day, the liver weight was completely recovered in both groups (P > 0.05).</p></span><span id="cesec100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle200">Pathological analysis</span><p id="para150" class="elsevierStylePara elsevierViewall">Liver parenchyma of control newborn rats showed a typical sinusoidal architecture and several extramedullary hematopoietic foci (<a class="elsevierStyleCrossRef" href="#fig5">Fig. 5</a>-1). Mitotic figures and apoptotic bodies were absent.</p><elsevierMultimedia ident="fig5"></elsevierMultimedia><p id="para160" class="elsevierStylePara elsevierViewall">On the first day after PH, hepatocyte nuclei of suckling animals were increased in size, with vesicular bodies and prominent nucleoli, but no mitosis was detected. On the second day, entire lobules were characterized by macrovesicular steatosis, which markedly decreased on the following day, when a few mitotic figures could be observed. Apoptotic bodies were rarely seen. On the fourth day, hepatocyte mitosis was still observed, and fatty infiltration was further diminished. Finally, on the seventh day after PH, the histological aspect of the liver was similar to controls (<a class="elsevierStyleCrossRef" href="#fig5">Fig. 5</a>-2 to 6).</p><p id="para170" class="elsevierStylePara elsevierViewall">Liver parenchyma of weaning control animals displayed similar architecture to the newborn animals, but no hematopoetic foci were evident (<a class="elsevierStyleCrossRef" href="#fig6">Figure 6-1</a>). On the first day after PH, their nuclei became vesicular with prominent nucleoli, and different phases of hepatocyte mitosis were observed throughout the lobule. On the second day, an increased number of hepatocyte mitoses were observed, although no steatosis was detected. Apoptotic bodies were rarely observed. From the third day, the number of hepatocyte mitoses decreased and could not be detected on the seventh day, when parenchymal architecture was completely recovered (<a class="elsevierStyleCrossRef" href="#fig6">Fig. 6</a>- 2 to 6).</p><elsevierMultimedia ident="fig6"></elsevierMultimedia><p id="para180" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRefs" href="#fig7">Figures 7 and 8</a> highlight hepatocyte mitosis and an apoptotic body, respectively.</p><elsevierMultimedia ident="fig7"></elsevierMultimedia><elsevierMultimedia ident="fig8"></elsevierMultimedia></span></span><span id="cesec110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle210">DISCUSSION</span><p id="para190" class="elsevierStylePara elsevierViewall">Despite the widespread use of <span class="elsevierStyleItalic">in vivo</span> models for biological phenomena studies, research on growing animals is rare. Models of pancreatic beta-cells regeneration in neonatal streptozotocin-treated rats<a class="elsevierStyleCrossRef" href="#bib12"><span class="elsevierStyleSup">12</span></a> and wound-healing studies in genetically modified newborn rats are rare examples of studies in growing animals.<a class="elsevierStyleCrossRef" href="#bib13"><span class="elsevierStyleSup">13</span></a></p><p id="para200" class="elsevierStylePara elsevierViewall">Anesthesia, respiratory depression, and frail and small sized organs, together with maternal cannibalism, represent severe difficulties in experiments with growing animals, especially newborns. Indeed, there was a significantly higher mortality rate in newborn animals relative to weaning animals (P = 0.003). Despite this fact, the creation of a newborn experimental model of hepatectomy and liver regeneration in rats (age 5-7 days) is important because these animals correspond to children weighing less than 5 kg. With the development and refinement of surgical techniques and microsurgical anastomoses, a series of liver transplants in such babies have been described and performed in centers throughout the world.<a class="elsevierStyleCrossRefs" href="#bib14"><span class="elsevierStyleSup">14,15</span></a> As a result, we conclude that learning about hepatic regeneration and remodeling mechanisms in newborns is of significant importance.</p><p id="para210" class="elsevierStylePara elsevierViewall">The weaning model resembles infants who have been submitted to partial liver transplantation at age 1-year, secondary to biliary atresia, which is the most common indication for hepatic transplantation in the pediatric population.<a class="elsevierStyleCrossRef" href="#bib11"><span class="elsevierStyleSup">11</span></a> Patients without biliary drainage after Kasai's procedure and non-operated children develop rapidly progressive cirrhosis, which necessitates liver transplantation within 6 to 18 months.<a class="elsevierStyleCrossRef" href="#bib16"><span class="elsevierStyleSup">16</span></a></p><p id="para220" class="elsevierStylePara elsevierViewall">Because it is technically difficult to create experimental models of liver transplantation using small growing animals, we developed the present experimental models to study molecular histomorphological and immunohistochemical mechanisms of liver regeneration. Although these models do not include liver transplantation, data obtained can be transposed to all conditions of liver parenchyma regeneration or liver size remodeling.</p><p id="para230" class="elsevierStylePara elsevierViewall">The daily assessment of remnant liver weight showed a gradual increase in hepatic mass from the first post-operative day until complete recovery by the seventh day. These results are similar to descriptions in adult rat models.<a class="elsevierStyleCrossRefs" href="#bib4"><span class="elsevierStyleSup">4,5,7</span></a> However, newborn animals exhibited a sharp increase in liver weight from the first to the second day after hepatectomy. Histological examination revealed intense fat accumulation in the liver parenchyma, resulting in weight gain. In addition, the increased number of hepatocyte mitoses observed after the third day reflects the high proliferative activity of liver cells during this phase.</p><p id="para240" class="elsevierStylePara elsevierViewall">During the early period of regeneration, the liver accumulates fat.<a class="elsevierStyleCrossRef" href="#bib17"><span class="elsevierStyleSup">17</span></a> Neither the mechanisms responsible for nor the functional significance of transient steatosis have been determined. In the current investigation, we observed that steatosis was more prominent in the newborn rat as compared to weaning rat livers. Interestingly, there are no descriptions of such fat accumulation in adult rat models of hepatectomy and liver regeneration. It is likely that the immaturity of the enzymatic systems of newborn hepatocytes promotes insufficient fat metabolism due to the increased metabolic demand of the remnant liver parenchyma.</p><p id="para250" class="elsevierStylePara elsevierViewall">Serial pathological analyses revealed that hepatocyte mitoses were more evident and earlier in the weaning animals than those observed in the newborn animals. Therefore, the initial liver weight gain in weaning animals was due to cellular proliferation, not steatosis; likewise, the proliferative activity of newborn hepatocytes, although slower, resulted in complete recovery of liver mass by the seventh day.</p></span><span id="cesec120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle220">CONCLUSIONS</span><p id="para260" class="elsevierStylePara elsevierViewall">The present investigation demonstrates that suckling and weaning rat models of partial hepatectomy are feasible and can be used to study liver regeneration. Serial weight and histological analysis revealed that, although similar, the process of hepatic regeneration in growing animals is different from adult animals, which highlights the need for a model to study this process in young, growing organisms. The models created and standardized in the present research will enable further elucidation of the mechanisms involved in liver regeneration, as well as the development of therapeutic interventions in this complex phenomenon.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xpalclavsec1585230" "titulo" => "KEYWORDS" ] 1 => array:3 [ "identificador" => "xres1815577" "titulo" => "RESUMO" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "ceabs50" "titulo" => "OBJETIVOS" ] 1 => array:2 [ "identificador" => "ceabs60" "titulo" => "MÉTODOS" ] 2 => array:2 [ "identificador" => "ceabs70" "titulo" => "RESULTADOS" ] 3 => array:2 [ "identificador" => "ceabs80" "titulo" => "CONCLUSÕES" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1585231" "titulo" => "UNITERMOS" ] 3 => array:2 [ "identificador" => "cesec10" "titulo" => "INTRODUCTION" ] 4 => array:3 [ "identificador" => "cesec20" "titulo" => "MATERIAL AND METHODS" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "cesec30" "titulo" => "Animals" ] 1 => array:2 [ "identificador" => "cesec40" "titulo" => "Creation of experimental models" ] 2 => array:2 [ "identificador" => "cesec50" "titulo" => "Histological analysis" ] 3 => array:2 [ "identificador" => "cesec60" "titulo" => "Statistical analysis" ] ] ] 5 => array:3 [ "identificador" => "cesec70" "titulo" => "RESULTS" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "cesec80" "titulo" => "Mortality rates" ] 1 => array:2 [ "identificador" => "cesec90" "titulo" => "Liver weight/body weight ratios following partial hepatectomy" ] 2 => array:2 [ "identificador" => "cesec100" "titulo" => "Pathological analysis" ] ] ] 6 => array:2 [ "identificador" => "cesec110" "titulo" => "DISCUSSION" ] 7 => array:2 [ "identificador" => "cesec120" "titulo" => "CONCLUSIONS" ] 8 => array:2 [ "identificador" => "xack640478" "titulo" => "ACKNOWLEDGMENT" ] 9 => array:1 [ "titulo" => "REFERENCES" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2007-06-28" "fechaAceptado" => "2007-08-24" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "KEYWORDS" "identificador" => "xpalclavsec1585230" "palabras" => array:5 [ 0 => "Liver regeneration" 1 => "Animal models" 2 => "Hepatectomy" 3 => "Newborn animals" 4 => "Rat" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "UNITERMOS" "identificador" => "xpalclavsec1585231" "palabras" => array:5 [ 0 => "Regeneração hepática" 1 => "Modelos animais" 2 => "Hepatectomia" 3 => "Animais recém-nascidos" 4 => "Rato" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">OBJECTIVES</span><p id="spara90" class="elsevierStyleSimplePara elsevierViewall">Liver regeneration is a complex process that has not been completely elucidated. The model most frequently used to study this phenomenon is 70% hepatectomy in adult rats; however, no papers have examined this effect in developing animals. The aims of the present study were: 1) to standardize two models of partial hepatectomy and liver regeneration in newborn suckling and weaning rats, and 2) to study the evolution of remnant liver weight and histological changes of hepatic parenchyma on the days that follow partial hepatectomy.</p></span> <span id="ceabs20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">METHODS</span><p id="spara100" class="elsevierStyleSimplePara elsevierViewall">Fifty newborn and forty-four weaning rats underwent 70% hepatectomy. After a midline incision, compression on both sides of the upper abdomen was performed to exteriorize the right medial, left medial and left lateral hepatic lobes, which were tied inferiorly and resected <span class="elsevierStyleItalic">en bloc.</span> The animals were sacrificed on days 0 (just after hepatectomy), 1, 2, 3, 4 and 7 after the operation. Body and liver weight were determined, and hepatic parenchyma was submitted to histological analysis.</p></span> <span id="ceabs30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">RESULTS</span><p id="spara110" class="elsevierStyleSimplePara elsevierViewall">Mortality rates of the newborn and weaning groups were 30% and 0%, respectively. There was a significant decrease in liver mass soon after partial hepatectomy, which completely recovered on the seventh day in both groups. Newborn rat regenerating liver showed marked steatosis on the second day. In the weaning rat liver, mitotic figures were observed earlier, and their amount was greater than in the newborn. CONCLUSIONS. Suckling and weaning rat models of partial hepatectomy are feasible and can be used for studies of liver regeneration. Although similar, the process of hepatic regeneration in developing animals is different from adults.</p></span>" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "ceabs10" "titulo" => "OBJECTIVES" ] 1 => array:2 [ "identificador" => "ceabs20" "titulo" => "METHODS" ] 2 => array:2 [ "identificador" => "ceabs30" "titulo" => "RESULTS" ] ] ] "pt" => array:3 [ "titulo" => "RESUMO" "resumen" => "<span id="ceabs50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle50">OBJETIVOS</span><p id="spara130" class="elsevierStyleSimplePara elsevierViewall">A regeneração hepática é um processo complexo não completamente elucidado. O modelo mais utilizado para o estudo desse fenômeno é a hepatectomia a 70% em ratos adultos. Não há trabalhos utilizando modelos em animais em crescimento. Desta forma, os objetivos deste estudo foram: 1. padronizar dois modelos de hepatectomia parcial e regeneração hepática utilizando ratos recém-nascidos e recém-desmamados; 2. estudar a evolução do peso do fígado remanescente e as alterações histológicas do parênquima hepático nos dias subseqüentes à hepatectomia parcial.</p></span> <span id="ceabs60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle60">MÉTODOS</span><p id="spara140" class="elsevierStyleSimplePara elsevierViewall">Cinqüenta ratos recém-nascidos e quarenta e quatro ratos recém-desmamados foram submetidos à hepatectomia a 70%. Após laparotomia mediana, foi realizada compressão bilateral no abdome superior do animal, levando à exteriorização dos lobos hepáticos direito medial, esquerdo medial e esquerdo lateral, que foram ligados na base e ressecados em bloco. Os animais foram sacrificados logo após a hepatectomia e no 1°,2°,3°,4°, e <span class="elsevierStyleItalic">7</span>° dias após a cirurgia. O peso corpóreo e do fígado foram determinados, e o parênquima hepático submetido à análise histológica.</p></span> <span id="ceabs70" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">RESULTADOS</span><p id="spara150" class="elsevierStyleSimplePara elsevierViewall">Os índices de mortalidade dos animais recém-nascidos e recém-desmamados foram 30% e 0% respectivamente. Em ambos os grupos, houve uma diminuição significativa na massa hepática logo após a hepatectomia, com recuperação completa no sétimo dia de pós-operatório. O parênquima hepático dos animais recém-nascidos apresentou acentuada esteatose no segundo dia. O fígado do animal recém-desmamado exibiu figuras mitóticas mais precoces e mais numerosas que o do recém-nascido.</p></span> <span id="ceabs80" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">CONCLUSÕES</span><p id="spara160" class="elsevierStyleSimplePara elsevierViewall">Os modelos de hepatectomia parcial em ratos recém-nascidos e recém-desmamados são factíveis e podem ser usados para estudos da regeneração hepática. Embora semelhante, o processo de regeneração hepática em animais em crescimento não é igual ao do animal adulto.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "ceabs50" "titulo" => "OBJETIVOS" ] 1 => array:2 [ "identificador" => "ceabs60" "titulo" => "MÉTODOS" ] 2 => array:2 [ "identificador" => "ceabs70" "titulo" => "RESULTADOS" ] 3 => array:2 [ "identificador" => "ceabs80" "titulo" => "CONCLUSÕES" ] ] ] ] "multimedia" => array:8 [ 0 => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 746 "Ancho" => 994 "Tamanyo" => 102743 ] ] "descripcion" => array:1 [ "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">Partial hepatectomy in newborn rat: liver, stomach and guts exteriorized by compression of the upper abdomen and the lateral inferior portions of the hemithorax bilaterally.</p>" ] ] 1 => array:7 [ "identificador" => "fig2" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 745 "Ancho" => 994 "Tamanyo" => 77362 ] ] "descripcion" => array:1 [ "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">A cotton ligature was passed between the liver and stomach.</p>" ] ] 2 => array:7 [ "identificador" => "fig3" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 682 "Ancho" => 990 "Tamanyo" => 49231 ] ] "descripcion" => array:1 [ "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">Schematic illustration of the parenchymal resection; detailed lateral view. The dark area indicates the parenchyma to be resected.</p>" ] ] 3 => array:7 [ "identificador" => "fig4" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 476 "Ancho" => 991 "Tamanyo" => 36704 ] ] "descripcion" => array:1 [ "en" => "<p id="spara40" class="elsevierStyleSimplePara elsevierViewall">Changes in the ratio of the remnant liver wet weight relative to body weight at varying timepoints after hepatectomy (for each group, n = 6-8 animals). Values are means ± SEM. (*significant; **nonsignificant in comparison to C – control group).</p>" ] ] 4 => array:7 [ "identificador" => "fig5" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1085 "Ancho" => 993 "Tamanyo" => 348772 ] ] "descripcion" => array:1 [ "en" => "<p id="spara50" class="elsevierStyleSimplePara elsevierViewall">Histological findings of control newborn rat livers and remnant livers on the days following PH. 1 is the control; 2, 3, 4, 5 and 6 correspond to 1, 2, 3, 4 and 7 days after PH, respectively (original magnification X 150 and 300). 1- Typical sinusoidal architecture, with several extramedullary hematopoietic foci (arrows). 2- Enlargement of hepatocyte nuclei with prominent nucleoli. 3- Intense macrovesicular steatosis. 4- Decrease in steatosis. 5- Mitotic figures in hepatocytes (arrows) and marked reduction of steatosis. 6- Histological aspect similar to control.</p>" ] ] 5 => array:7 [ "identificador" => "fig6" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1085 "Ancho" => 994 "Tamanyo" => 344844 ] ] "descripcion" => array:1 [ "en" => "<p id="spara60" class="elsevierStyleSimplePara elsevierViewall">Histological findings of the liver of control weaning rat and remnant liver on days following PH. 1 is the control; 2, 3, 4, 5 and 6 correspond to 1, 2, 3, 4 and 7 days after PH (original magnification X 150 and 300). 1- Typical sinusoidal architecture. 2- Enlargement of hepatocyte nuclei with prominent nucleoli. 3- Mitotic figures in different phases (arrows) and no steatosis. Since the third day (4), parenchimal architecture becomes histologically similar to control (5 and 6).</p>" ] ] 6 => array:7 [ "identificador" => "fig7" "etiqueta" => "Figure 7" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr7.jpeg" "Alto" => 696 "Ancho" => 994 "Tamanyo" => 202634 ] ] "descripcion" => array:1 [ "en" => "<p id="spara70" class="elsevierStyleSimplePara elsevierViewall">Photomicrograph of a weaning rat liver on the second day after PH, with hepatocyte mitoses (arrow) (original magnification X 1500, under oil immersion).</p>" ] ] 7 => array:7 [ "identificador" => "fig8" "etiqueta" => "Figure 8" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr8.jpeg" "Alto" => 784 "Ancho" => 994 "Tamanyo" => 209163 ] ] "descripcion" => array:1 [ "en" => "<p id="spara80" class="elsevierStyleSimplePara elsevierViewall">Photomicrograph of a weaning rat liver on the first day after PH, with an apoptotic body. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 21 | 8 | 29 |
| 2024 September | 44 | 20 | 64 |
| 2024 August | 49 | 18 | 67 |
| 2024 July | 32 | 25 | 57 |
| 2024 June | 30 | 15 | 45 |
| 2024 May | 46 | 13 | 59 |
| 2024 April | 43 | 12 | 55 |
| 2024 March | 36 | 9 | 45 |
| 2024 February | 54 | 17 | 71 |
| 2024 January | 51 | 9 | 60 |
| 2023 December | 28 | 16 | 44 |
| 2023 November | 23 | 22 | 45 |
| 2023 October | 14 | 11 | 25 |
| 2023 September | 13 | 21 | 34 |
| 2023 August | 5 | 5 | 10 |
| 2023 July | 4 | 8 | 12 |
| 2023 June | 2 | 0 | 2 |
| 2023 May | 0 | 3 | 3 |
| 2023 April | 1 | 1 | 2 |
| 2023 March | 2 | 0 | 2 |
| 2023 February | 0 | 1 | 1 |
| 2023 January | 0 | 0 | 0 |
| 2022 December | 48 | 2 | 50 |
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