HFJ和Wistar大鼠脂肪肝及胰岛素抵抗动物模型的比较

目的建立近交系HFJ大鼠和封闭群Wistar大鼠脂肪肝胰岛素抵抗动物模型及比较其生物学特性。方法雄性HFJ大鼠和Wistar大鼠,分别随机分为模型组和正常组,模型组喂养高脂饮食,正常组喂养普通饮食,两组脂肪分别占摄入能量的44.2%和19.2%,共饲养12周。每周称体质量,测定血糖、甘油三酯、胆固醇、ALT、AST、HDLC、LDLC和血胰岛素水平。实验期末处死动物摘取肝脏并称质量,计算肝指数;鼠肝脏用10%甲醛固定,石蜡包埋切片,HE染色,光镜下评估肝脂肪变性和炎症活动情况。结果镜下可见,HFJ和Wistar大鼠模型组肝细胞均呈现弥漫性脂肪变性,小叶内可见炎症细胞浸润,HFJ比Wistar脂肪变性较重,对照组肝脏均未见异常。两种动物的模型组ALT、AST、肝指数、HOMA-IR指数均显著高于其正常组,HFJ和Wistar种系间各指标的差异无显著性;HFJ大鼠模型组体重和正常组体重具有显著性差异(P<0.01),而Wistar大鼠模型组体重与正常组体重间无显著差异(P>0.05);HFJ大鼠TG和TC含量均显著高于Wistar大鼠。结论通过高脂饮食喂养成功建立了HFJ大鼠和Wistar大鼠脂肪肝与胰岛素抵抗疾病动物模型,与Wistar大鼠比较,HFJ大鼠具有自发性高血脂特征,造模更易成功,可为胰岛素抵抗和脂肪肝的发病机制研究、防治高血脂药物筛选提供一种新的实验动物。

Comparison of the Fatty Liver and Insulin Resistance Animal Model in HFJ Inbred Rats and Wistar Closed Colony Rats

Objective To establish fatty liver and insulin resistance animal model in HFJ inbred rats and Wistar closed colony rats,and compare their biological characteristics.Methods Male HFJ rats and Wistar rats were randomly divided into model group and control group,which were fed with high-fat diet(44.2% of energy from fat) and standard diet(19.2% of energy from fat) respectively for 12 weeks.All rats were weighed every week.Fasting blood glucose,alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),total cholesterol(TC),HDLC,LDLC and fast insulin were tested by drawing blood from left ventricular.Liver wet weights were measured by freeing liver,and calculated liver index.Rat liver was fixed with 10% formalin and embedded with paraffin.Assessment of hepatic steatosis and inflammation in all rats is measured under light microscope by HE stain.Results Liver tissue pathology showed that the hepatic cells of model group of HFJ and Wistar rats presented diffused macrovesicular steatosis and lobular inflammatory cell infiltration,and HFJ rats were more serious than Wistar rats.Rats in control group showed no abnormal.All rats in model group had elevated levels of AST,ALT,liver index and HOMA-IR,and there was no significant difference between HFJ rats and Wistar rats.Body weigh of the model group of HFJ rats were higher than those in control group(P<0.01),and there were no significant differences between model group and control group of Wistar rats(P>0.05).Serum TG and TC of the HFJ rats were obviously higher than that of Wistar rats.Conclusion A fatty liver and insulin resistance model was successfully developed in HFJ inbred rats and Wistar rats by high-fat diet method.Compared with Wistar rats,HFJ rats had spontaneously high blood lipid characteristics,which provided a useful experimental tool for elucidating pathogenesis and treatment of fatty liver.