利莫那班改善KKAy小鼠糖脂代谢与外周CB1受体表达的初步研究

摘要

目的 探讨利莫那班改善KKAy小鼠糖、脂代谢紊乱与外周组织CB1受体(CB1R)表达的关系.方法 10周龄C57BL/6J和KKAy小鼠各分两组,分别灌胃给予溶剂和10 mg/kg利莫那班,1次/d,共计26 d.给药期间每天测定小鼠体质量,给药20 d时测空腹血糖,实验结束时测定血清甘油三酯(TG)、总胆固醇(TC);采用Multiplex法测定血清胰岛素、瘦素和脂联素含量;测定小鼠肝体、脂体系数,并对肝脏和附睾脂中CB1R表达进行免疫印迹法分析.结果 (1)KKAy小鼠糖、脂代谢明显紊乱.利莫那班特异性地改变KKAy小鼠的特征,如降低空腹血糖(P<0.05);降低血清TC水平(P<0.05)、血清胰岛素(P<0.01)并升高血清脂联素水平(P<0.05);减轻体质量、降低肝体和脂体系数(P<0.05),对C57小鼠无影响.(2)KKAy小鼠肝脏CB1R的表达水平显著低于C57小鼠(P<0.01),而附睾脂CB1R表达水平显著高于C57小鼠(P<0.01),附睾脂中CB1R表达水平达肝脏的6倍以上.(3)利莫那班可显著降低KKAy小鼠肝脏(P<0.05)和附睾脂CB1R的表达(P<0.01),而对C57小鼠肝脏和附睾中CB1R表达的作用较弱.结论 利莫那班能够改善KKAy小鼠糖、脂代谢紊乱,该作用与其降低外周组织尤其是附睾脂中CB1R表达相关.%Objective To investigate the relationship between the improvement of glucose and lipid disorders in KKAy mice by rimonabant and the expression of CB1 receptor ( CB1R) in peripheral tissues.Methods Ten-week-old C57BL/6J and KKAy mice were randomly divided into two groups respectively: the vehicle control group and rimonabant (10 mg/kg)treatment group (n = 8).The mice were treated for 26 days.Changes in body mass were monitored every day and fasting blood glucose was tested on the 20th day of treatment.At the end of the experiment, serum triglyceride (TG), total cholesterol (TC), insulin, leptin and adiponeetin concentrations were determined.Liver and total fat parameters were weighed.The expression of CB1R in the liver and epididymal fat were determined by Western blot.Results ( 1 ) KKAy mice displayed characteristics of T2DM: with dysfunctions in blood glucose and lipids metabolism.Rimonabant could specifically ameliorate some dysfunctions of KKAy mice, as evidenced by the decreasing glucose, serum TC and insulin level, increasing serum adiponectin, and reducing body mass, liver and adipose weight index, but it had no these effect on C57 mice.(2) The expression of CB1R in the liver of KKAy mice significantly lowered, but remarkably higher than that of C57 mice in epididymal fat.The expression of CB1R in the epididymal fat of KKAy mice was six times more than that in the liver.(3) Rimonabant could significantly reduce CB1R expression in these tissues of KKAy mice.However, for the normal C57 mice, the effect on CB1R expression was slight.Conclusion Rimonabant could effectively ameliorate the metabolic disorders of glucose and lipid in KKAy mice, which is correlated with the down-regulated expression of CB1 receptor in the liver and especially in the epididymal fat of KKAy mice.