胰高血糖素样肽用于大鼠减肥的长期疗效

Long-term Effect of Exendin-4 on Weight Reduction of Normal Rats

目的研究胰高血糖素样肽（exendin-4）长期皮下给药的减重效果。方法将160只6～8周Wistar大鼠。随机分成4组，每组40只，其中一组为对照组，另外三组分别皮下注射小、中和大剂量（1、5和25μg／kg）exendin-4，连续26周。记录体重和摄食量，并进行血清胆固醇、甘油三酯检测，测定腹膜后肾周围脂肪重量和细胞大小。结果与对照组比较，大剂量用药后大鼠体重增长缓慢（P＜0．01），腹膜后肾周围脂肪重量显著降低（P＜0．05），血清甘油三酯水平降低（P＜0．01），而摄食量、血清胆固醇含量和脂肪细胞大小不受药物的影响。结论25μg／kg exendin-4长期皮下给药，具有明确的延缓体重增长的效果，其作用机制可能与抑制脂肪细胞的增殖有关，而与抑制食欲无关。

Objective To study the effect of exendin-4 on weight reduction after long-term subcutaneous injection. Methods Totally 160 Wistar rats （6-8 weeks） were randomly divided into four groups with 40 in each group. One of them was control group, and the other three were given subcutaneous injection with low, medium, and high doses （ 1, 5, and 25 μg/kg） exendin-4, respectively for 26 weeks. Body weight and food intake were recorded, serum cholesterol, triglyceride, and weight and diameter of retroperitoneal lipocytes surrounding kidneys were measured. Results Body weight （P 〈 0. 01 ）, fat weight （ P 〈 0. 05 ）, and serum triglyceride level （P 〈0. 01 ） in 25 μg/kg exendin-4 group were significantly lower than those in control group. Food intake, serum cholesterol, and lipocytes diameter were not influenced after administration of exendin-4. Conclusion Long-term subcutaneous injection of high dose exendin-4 （25 μg/kg） has obvious inhibitory effect on weight growth probably through restraining the proliferation of lipocytes and not suppressing the appetite.