利莫那班改构物对高脂饮食诱导肥胖小鼠的减肥效应及机制

摘要

目的:从新合成的利莫那班改构物中筛选对饮食诱导的肥胖小鼠具有减肥作用的化合物,探讨其减肥效应及机制.方法:采用放射性受体配体结合试验测定利莫那班改构物对CB1受体的IC50,高脂饮食法诱导建立肥胖小鼠模型,给予改构物ZH 10 mg/kg和30 mg/k治疗4周,检测体质量变化以及生殖器周围脂肪含量、脂肪细胞形态和血清胆固醇、三酰甘油含量的变化.结果:改构物ZH对CB1受体具有抑制作用,可显著减少小鼠的食物摄入量和体质量,降低生殖器周围脂肪、血清胆固醇及三酰甘油的含量.结论:ZH可通过抑制CB1受体,降低食欲产生减肥作用,同时能降低血脂水平.%Objective: A series of analogues of rimonabant were synthesized to investigate their lose-weight effect and mechanisms. Methods: The IC50 of analogues on the CB1 were determined by Radioactive-ligand receptor binding assay, male ICR mice were fed with high fat diet to build the obese mice model and treated with 10 mg/kg or 30 mg/kg ZH per day for 4 weeks. Body weight and the content/morphology of genital peripheral adipose tissue were detected, the content of total cholesterol (TC) and triacylglycerol (TG) in serum were also estimated. Results; ZH had the inhibition on the CB1, it could significantly reduce the food intake and body weight, the content of genital peripheral adipose tissue, TC and TG in serum were reduced. Conclusion; ZH could suppress the CB1, ZH reduced the weight through inhibiting appetite and blood lip-id levels.