Establishment of a rat model of nonalcoholic steatohepatitis and histopathological changes of the pancreas and the kidney

Objective To establish a rat model of nonalcoholic steatohepatitis,and to investigate the histopathological changes of the extrahepatic organs of the pancreas and the kidney. Methods A total of 20 Sprague-Dawley rats were selected,among which 6 were randomly selected as the observation group(group B). The remaining 14 rats were paired into seven groups according to body weight,then a random number table was used to select 1 rat from each group and assign them into the experimental group(group C),and the remaining 7 rats were assigned to the control group(group A). The rats in groups B and C were given high-fat diet,while those in group A were given a normal diet. In group B,two rats each were killed at weeks 4,8,and 12 of the experiment,liver tissue was extracted for HE staining,and liver pathological sections were observed under a microscope to see whether steatohepatitis was achieved. The model was successfully established at the end of week 12. All rats in groups A and C were sacrificed,and the serological markers alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transpeptidase(GGT),triglyceride(TG),total cholesterol(TC),low-density lipoprotein(LDL),glucose(GLU),insulin(INS),and homeostasis model assessment of insulin resistance(HOMA-IR) were measured. HE staining was performed for liver tissue and pancreatic tissue to observe the changes in pancreatic acini and pancreatic islets. PAS staining was performed for kidney tissue,and immunohistochemical desmin-staining was performed to observe the expression of desmin in glomerular podocytes. The t-test was used for comparison of continuous data between two groups. Results Compared with group A,group C had significantly higher pathological score and serum levels of ALT,GGT,LDL,TG,TC,GLU,INS,and HOMA-IR(t = 4. 67,2. 83,2. 34,4. 58,4. 78,3. 00,2. 97,3. 80 and 4. 10,all P < 0. 05). Liver pathological changes were observed in the high-fat group from week 4 to week 12,i. e.,the lobular structure was gradually destroyed,the small fat vacuoles in the cytoplasm of the hepatocytes gradually developed into large fat vacuoles,and inflammatory cell infiltration gradually appeared in the portal area. Pancreatic pathological changes were observed in the high-fat group at the end of week 12,i. e.,apoptosis and atrophy of pancreatic acinar cells were observed,and no significant abnormalities were observed in pancreatic islet cells. Renal pathological changes were observed in the high-fat group at the end of week 12,i. e.,therewere significant increases in the substances with positive PAS staining results,the glomerular volume,and the thickness of the glomerular capillary basement membrane,with disordered arrangement of capillary loops,hyperplasia of the mesangial area,swelling of renal tubular epithelial cells,and stenosis of some lumens. Immunohistochemical staining showed an increase in the expression of desmin in glomerular podocytes in the high-fat group. Conclusion A rat model of nonalcoholic steatohepatitis is successfully established by high-fat diet.Nonalcoholic steatohepatitis in rats may lead to apoptosis and atrophy of pancreatic acinar cells,increase in glomerular volume,thickening of the capillary basement membrane,mesangial hyperplasia,and podocyte injury.