利莫那班衍生物对高脂肥胖模型小鼠的减肥作用

［摘要］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。

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

Abstract]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 administration per day for 18 days. Body weight and the content/morphology of genital peripheral adipose tissue and morphology of liver were detected, the content of total cholesterol,triacylglycerol,high density lipoprotein 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.