利拉鲁肽对高脂饮食喂养大鼠的血脂谱的调节作用

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[摘要] 目的 研究利拉鲁肽对高脂饮食喂养SD大鼠脂肪代谢的影响。 方法 将48只雄性SD大鼠随机分为四组，分别予以普通饮食（ND）、高脂饮食（HFD）、高脂饮食加小剂量利拉鲁肽腹腔注射（HFD+SGLP-1）、高脂饮食加大剂量利拉鲁肽腹腔注射（HFD+LGLP-1）。喂养8周后检测大鼠血脂、血糖、体重，并检测大鼠肝脏ApoE蛋白表达水平的变化。 结果 与ND组比较，HFD组大鼠体重、血脂及血糖水平显著升高，肝脏ApoE蛋白水平显著降低（P ＜ 0.05）。而与HFD组比较，HFD+SGLP-1组和HFD+LGLP-1组大鼠体重、血脂及血糖水平明显降低，ApoE蛋白水平明显增高（P ＜ 0.05），但以HFD+LGLP-1组效果最为显著。 结论 利拉鲁肽能够显著抑制高脂饮食喂养导致的体重增加，降低血糖及血脂水平，并调节血脂谱。利拉鲁肽改变血脂谱的作用可能与其增加肝脏ApoE蛋白的表达有关。

[关键词] 利拉鲁肽；高脂饮食；调节；血脂谱

[中图分类号] R969.4 [文献标识码] A [文章编号] 1673-7210（2012）07（a）-0016-02

Effects of Liraglutide on the lipid profile in high-fat diet rats

HONG Tao TU Jing DONG Yanhua ZHONG Jing WEN Fang WEN Gebo

Department of Endocrinology, the First Affiliated Hospital of University of South China, Hu'nan Province, Hengyang 421001, China

[Abstract] Objective To investigate the anti-hyperlipidemia effect of Liraglutide on high-fat diet SD rats and its mechanism. Methods Fourty eight male SD rats were randomly separated into four groups accordding to body weight. They were respectively fed with normal diet (ND), high-fat diet (HFD), high-fat diet with small doses of Liraglutide injected intraperitoneally (HFD+SGLP-1), high-fat diet with large doses of Liraglutide injected intraperitoneally (HFD+LGLP-1). After 8 weeks, the body weight, blood sugar level and lipid profile were measured, the change of ApoE protein expression level in liver were detected by western blot. Results Compared with those in ND group, the body weight, blood-fat level and blood sugar level of HFD group increased significantly, and the ApoE level decreased significantly (P ＜ 0.05). Compared with HFD group, there were significantly lower for the body weight, blood-fat level and blood sugar level and significant high for the ApoE level of HFD+SGLP-1 group and HFD+LGLP-1 group (P ＜ 0.05). But the effect of HFD+LGLP-1 group was most pronounced. Conclusion Liraglutide can obviously restrain high-fat diet induced over-weight, reduce blood-fat and blood sugar levels and regulate lipid profile. The regulatory function of change lipid profile may have a relationship with the improvment of ApoE protein expression in liver.

[Key words] Liraglutide; High-fat diet; Regulate; Lipid profile

随着现代医学的发展，人们对2型糖尿病的研究日渐深入，发现通过口服葡萄糖对促进胰岛素分泌的疗效远远超过静脉注射，这种效应被称作“肠促胰素效应”[1]。而2型糖尿病的发病机制之一很有可能是人体内的肠促胰素效果减退。肠促胰素是人体内一种肠源性激素，进食后，此类激素可促进胰岛素的分泌，发挥葡萄糖浓度依赖性降糖作用和降脂作用。肠促胰素主要由胰高糖素样肽-1（glucagon-like peptide-1，GLP-1）和葡萄糖依赖性胰岛素释放肽（glucose dependent insulinotropic peptide，GIP）组成，而前者在2型糖尿病发生发展中的作用又更为重要。利拉鲁肽是一种治疗2型糖尿病的长效GLP-1类似物，其可以通过血脑屏障，改善由高脂饮食引起的高脂血症、体重增加、血糖升高及胰岛素抵抗作用[2]。现报道如下：