高脂饮食构建胰岛素抵抗脂肪肝大鼠模型

目的通过高脂饮食构建非酒精性脂肪肝病（NAFLD）大鼠模型；分析胰岛素抵抗（IR）在NAFLD形成过程中的作用。方法将48只雄性SD大鼠随机分为正常饮食组（NG）及高脂饮食组（FG）各24只。第2、4、6、8周末时，2组各随机抽取6只，称体重，测空腹血糖、空腹胰岛素、甘油三酯、总胆固醇、丙氨酸氨基转移酶和天门冬氨酸氨基转移酶，并计算空腹胰岛素抵抗指数；然后计算肝指数（肝湿重（g）／体重（g）×100％）；制备肝组织匀浆测丙二醛、超氧化物歧化酶以及光镜检查肝组织切片以评价肝脏脂肪变性程度。结果FG组大鼠的体重增长比NG组快；肝指数在第2、4、6、8周末均大于NG；第2周末时已出现肝细胞脂肪变，其程度随喂养时间的延长逐渐加重，第4周末开始出现IR、高TG、TC血症、肝脏转氨酶异常及肝脏脂质过氧化损害，第6周末时形成轻度脂肪肝，第8周末时发展为中度脂肪肝。结论SD大鼠用改良型高脂饲料持续喂养6周可形成伴有IR的NAFLD，IR在NAFLD的发生发展中有重要作用。

Construct a rat model of nonalcoholic fatty liver disease with insulin resistance by feeding ruts fat-rich diet

Objective To construct a rat model of nonalcoholic fatty liver disease (NAFLD) by feeding rats fat-rich diet and analyze the effect of insulin resistance (IR)in the development of NAFLD. Methods Male SD rats were randomly divided into normal diet group (NG, n =24) and fat-rich diet group (FG, n =24). At the end of feeding for2 weeks, 4 weeks, 6 weeks or 8weeks, 6 rats in NG and FG were randomly took out. Their weight were recorded, then the serum fasting blood sugar, fasting insulin, triglyceride, total cholesterol, ala-nine aminotransferase and aspartate aminotransferase were measured, and the fasting insulin resistance index and liver index (liver weight (g)/body weight(g) × 100%)was calculated. Then liver tissues were homogenized, and muleic dialdehyde and superoxide dismutase were determined. The hepatic steatosis in all rats was assessed according to the results under light microscope. Results The body weight of rats in NG increased faster than those in FG after six weeks. The liver index of rats in FG was markedly higher than that in NG since the second weekend. The rats in FG began to have hepatocyte steatosis from the second weekend, had insulin resistance, hyperlipidemia, dysfunction of liver and lipid peroxide of liver from the fourth weekend, suffered mild fatty liver from the sixth weekend, and developed to moderate fatty liv-er from the eighth weekend. Conclusions NAFLD with IR model was successfully developed by feeding SD rats with an improved rich-fat diet for 6 weeks. IR may play an important role in the development of NAFLD.