E2HSA对老龄肥胖小鼠糖脂代谢和β细胞功能的影响

发布时间：2018-09-17 08:46

【摘要】：目的:评价GLP-1受体激活剂E2HSA对老龄肥胖模型动物糖脂代谢和胰岛β细胞功能的影响。方法:12月龄肥胖MSG小鼠每天皮下注射E2HSA(1,3和9 mg·kg~(-1)),连续46 d。动态测定小鼠随机血糖、空腹血糖、口服葡萄糖耐量、血甘油三酯(TG)和总胆固醇(TC)水平;进行高血糖钳夹实验研究以评价胰岛β细胞功能;同时动态测定血清抗体滴度并分析其与药效变化的关系。结果:E2HSA在1~9 mg·kg~(-1)剂量下能够明显降低MSG小鼠的随机血糖、血TG和TC水平,降低空腹血糖和改善口服葡萄糖耐量异常,但随着给药时间的延长,作用逐渐减弱;能显著增加葡萄糖输注速率(GIR)和胰岛素最大分泌能力;E2HSA长期给药能使小鼠产生抗体,且随着给药时间的延长,抗体滴度逐渐升高,这可能是药效作用变化的主要原因。结论:E2HSA长期给药能够改善老龄肥胖MSG小鼠的糖脂代谢和胰岛β细胞功能。
[Abstract]:Aim: to evaluate the effects of GLP-1 receptor activator (E2HSA) on glycolipid metabolism and islet 尾-cell function in aged obese rats. Methods obese MSG mice of 12 months old were subcutaneously injected with E2HSA (1 mg kg~ 3 and 9 mg kg~ 1), for 46 days). The levels of random blood glucose, fasting blood glucose, oral glucose tolerance, serum triglyceride (TG) and total cholesterol (TC) were determined dynamically, and the function of islet 尾 cells was evaluated by hyperglycemic clamp test. At the same time, the titer of serum antibody was determined dynamically and the relationship between antibody titer and pharmacodynamics was analyzed. Results at the dose of 1 ~ 9 mg kg~ (-1), WE2HSA could significantly reduce the levels of random blood glucose, serum TG and TC, decrease fasting blood glucose and improve oral glucose tolerance in MSG mice, but with the prolongation of administration time, the effect gradually weakened. E2HSA could significantly increase the glucose infusion rate (GIR) and the maximum insulin secretion ability. The antibody titer increased with the prolongation of administration time, which may be the main reason for the change of pharmacodynamics. Conclusion long term administration of WE2HSA can improve glucose and lipid metabolism and islet 尾 -cell function in aged obese MSG mice.
【作者单位】：中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室;
【基金】：国家“重大新药创制”科技重大专项资助项目(2012ZX09301002)
【分类号】：R589.2

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