非酒精性脂肪性肝炎大鼠模型的建立及其胰腺、肾脏的组织学病理变化  

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

作　　者：宋清莲 谭玉娥[1] 刘京京 袁贝贝 李敏[1] 贺礼琴 戴光荣[1] SONG Qinglian;TAN Yu’e;LIU Jingjing(Department of Gastroenterology,Yan’an University Affiliated Hospital,Yan’an,Shaanxi 716000,China)

机构地区：[1]延安大学附属医院消化内科

出　　处：《临床肝胆病杂志》2020年第1期140-144,共5页Journal of Clinical Hepatology

基　　金：陕西省社会发展科技攻关项目(2016SF-120)

摘　　要：目的探讨非酒精性脂肪性肝炎大鼠模型肝外脏器胰腺、肾脏的组织学病理变化情况。方法将20只SD大鼠中的6只首先按完全随机配对分配到观察组(B组),将剩下的14只按体质量配对成7个区组,最后将每个区组中的1只大鼠按随机数字表分配到实验组(C组),其余7只为对照组(A组)。B组和C组给予高脂饮食,A组给予普通饮食。B组于实验第4、8、12周各处死2只,提取肝脏组织行HE染色,显微镜下观察肝脏病理切片是否达到脂肪性肝炎,第12周末建模成功(提示C组建模成功)。处死A组和C组全部大鼠,分别检测血清学指标ALT、AST、GGT、TG、TC、LDL、GLU、INS、HOMA-IR,取肝脏组织行HE染色;胰腺组织行HE染色观察大鼠胰腺腺泡和胰岛变化情况;肾脏组织行PAS染色,免疫组织化学desmin蛋白染色观察肾小球和足细胞desmin表达情况。计量资料2组间比较采用t检验。结果C组大鼠病理评分及血清ALT、GGT、LDL、TG、TC、GLU、INS、HOMAIR水平均高于A组(t值分别为4.67、2.83、2.34、4.58、4.78、3.00、2.97、3.80、4.10,P值均<0.05)。高脂组从第4周开始到第12周末肝脏病理改变为:肝小叶结构逐渐破坏,肝细胞胞浆内的小脂肪空泡逐渐转变为大脂肪空泡,汇管区逐渐出现炎症细胞浸润。高脂组第12周末胰腺病理改变为:胰腺腺泡细胞开始出现凋亡,萎缩,胰岛细胞未见明显异常。高脂组第12周末肾脏病理改变为:PAS染色阳性物质明显增多,肾小球体积增大,肾小球毛细血管基底膜增厚,毛细血管袢排列紊乱,系膜区增生明显;肾小管上皮细胞肿胀,部分管腔狭窄。高脂组肾组织免疫组化:肾小球足细胞desmin表达增强。结论高脂饮食诱导大鼠成功构建大鼠非酒精性脂肪性肝炎模型;大鼠非酒精性脂肪性肝炎模型可能导致胰腺腺泡细胞凋亡、萎缩;肾脏肾小球体积增大,毛细血管基底膜增厚,系膜增生,足细胞损伤。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 hepa

关 键 词：非酒精性脂肪性肝炎 大鼠 Sprague-Dawley 胰腺 肾脏 组织和显徽镜检结果 

分 类 号：R575.5[医药卫生—消化系统] R576[医药卫生—内科学]