利莫那班衍生物对高脂肥胖模型小鼠的减肥作用

Lose-weight effect on high fat diet-induced obese mice of analogues of rimonabant ZH-101-S

目的:观察利莫那班衍生物ZH-101-S对高脂饲料饲喂小鼠的减肥作用。方法:以高脂饲料喂养ICR雄性小鼠1月建立高脂肥胖模型。将小鼠随机分为5组,对照组、高脂模型组、利莫那班30 mg/kg组、ZH-101-S 10 mg/kg组和ZH-101-S 30 mg/kg组。正常组和模型组给予0.5%的羧甲基纤维素钠,其他3组分别给予相应的药物,各组均连续灌胃给药18 d。实验过程中测量小鼠体质量,末次给药后空腹12 h,眼眶采血检测小鼠空腹血清总胆固醇、三酰甘油、高密度脂蛋白胆固醇(HDL-C)、血糖、极低密度脂蛋白胆固醇(LDL-C)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、乳酸脱氢酶(LDH)水平。处死小鼠,取附睾脂肪称重并计算脂肪系数(附睾脂肪质量/净体重),并将脂肪及肝脏组织进行切片和HE染色。结果:连续给药18 d后ZH-101-S组小鼠体质量、血清总胆固醇、三酰甘油、血糖、LDL-C、AST、ALT、LDH水平均明显低于模型组(P<0.05),HDL-C较模型组明显升高;光镜下,ZH-101-S组脂肪细胞直径、肝组织脂滴空泡数均明显小于或少于模型组。结论:利莫那班衍生物ZH-101-S在减轻高脂肥胖模型小鼠体质量的同时能降低血脂水平,改善肝损伤。

Objective： To investigate the mechanism of analogues of rimonabant ZH-101-S lose-weight effect on high-fat diet-induced obese mice. Methods： Male ICR mice were fed with high fat diet to build the obese mice model and the mice were divided into control group, obese model group, rimonabant group （30 mg/kg）and ZH-101-S group （15 mg/kg, 30 mg/kg）. All drug were administered by intragastric ad- ministration per day for 18 days. Body weight and the content/morphology of genital peripheral adipose tis- sue and morphology of liver were detected, the content of total cholesterol, triacylglycerol, high density lipo- protein cholesterol （ HDL-C ）, glucose, low density lipoprotein cholesterol （ LDL-C ）, glutamic-oxalacetic transaminase （ AST）, glutamic-pyruvic transaminase （ALT） and lactic dehydrogenase （LDH） in serum were also estimated. Results： After treated with ZH-101-S for 18 days, the bodyweight of mice and the content of genital peripheral adipose tissue were significantly reduced, compared with model group. ZH-101-S could decrease the level of triacylglycerol,total cholesterol,LDL-C, LDH in serum and elevate the level of HDL- C. Finally, ZH-101-S protected high fat food induced hepatic injury proved by AST and ALT decrease and improvement of liver morphology. Conclusion： ZH-101-S could reduce the bodyweight, improve plasma lipid profile and hepatic injury of high-fat diet-induced obese mice.