利拉鲁肽对动脉硬化大鼠模型的疗效评价

Efficacy of liraglutide on atherosclerotic rat model

目的根据血管张力、血管病理及血清学指标来评价利拉鲁肽治疗高脂诱导动脉硬化大鼠模型的疗效。方法32只SPF级雄性大鼠,随机分为高脂组20只、对照组12只。将造模成功的高脂组随机分为利拉鲁肽组和安慰剂组,并继续给予高脂饲料喂养,同时分别皮下注射利拉鲁肽或生理盐水,对照组继续给予普通饲料喂养。干预16周末,检测血清三酰甘油(TG)、总胆固醇(CHO)、低密度脂蛋白(LDL)、空腹血糖(FBG)、空腹胰岛素(FINS)水平,检测血清一氧化氮(NO)和内皮素1(ET-1)水平评价血管内皮功能改变;血管组织HE染色及Masson染色观察血管壁改变;血管张力检测仪检测各组大鼠血管张力变化。采用方差齐性检验分析实验数据。结果与安慰剂组相比,利拉鲁肽组大鼠血清TG、CHO、LDL、FINS、ET-1水平均明显下降(P<0.05),NO水平升高(P<0.05);血管病理结果显示血管内皮损伤程度显著减轻,血管平滑肌细胞增殖及迁移减少;血管张力检测结果显示利拉鲁肽组血管舒张功能显著改善(P<0.05)。结论利拉鲁肽能明显减轻高脂饮食诱导的动脉硬化大鼠的血管内皮损伤,保护内皮细胞,抑制平滑肌细胞增殖及迁移,有可能成为改善动脉硬化程度的新药物。

Objective The curative effect of liraglutide on rat model of atherosclerosis induced by high fat was evaluated according to vascular tone,vascular pathology and serological indexes. Methods Thirty SDF male rats were randomly divided into high fat group（ n = 20） and control group（ n = 12）. The successful model of high fat group were randomly divided into liraglutide group and placebo group,and continue to be given high-fat diet,respectively,while subcutaneous injection of liraglutide or saline,the control group continue to be fed ordinary feed.At the end of the 16 th week of intervention,serum triglyceride（ TG）,total cholesterol（ CHO）,low density lipoprotein（ LDL）,fasting blood glucose（ FBG） and fasting insulin（ FINS） were measured; the changes of vascular endothelial function were evaluated by the level of serum nitric oxide（ NO） and endothelin 1（ ET-1）; the vascular wall was observed by HE staining and Masson staining; the vascular tension was detected by aorta-ring apparatus.The data were analyzed by means of homogeneity of variance. Results Compared with placebo group,the levels of serum TG,CHO,LDL,FINS and ET-1 in liraglutide group were significantly decreased（ P 〈 0. 05） and NO levels were increased（ P 〈 0. 05）; the results of vascular pathology showed that the degree of vascular endothelial injury was significantly reduced and the proliferation and migration of vascular smooth muscle cells were decreased; the results of aorta-ring results showed that the vasodilation of liraglutide group was significantly improved（ P 〈 0. 05）.Conclusion liraglutide can significantly reduce the vascular endothelial injury induced by high-fat diet,protect endothelial cells and inhibit the proliferation and migration of smooth muscle cells,which may become a new drug to improve the degree of atherosclerosis.