西格列汀对ApoE^(-/-)小鼠动脉粥样硬化病变的影响

Effect of sitagliptin on atherosclerosis in ApoE^(-/-) mice

目的探讨二肽基肽酶-4(DPP-4)抑制剂西格列汀对动脉粥样硬化的影响及其机制。方法将30只雄性载脂蛋白E基因敲除(ApoE^(-/-))小鼠随机分为对照组(n=15)和实验组(n=15),对照组给予高脂饮食,实验组小鼠进行高脂饮食并予以沙格列汀灌胃。16周后,眼球取血,分析血清中血脂和血糖水平,ELISA方法检测血清中一氧化氮合酶(e NOS)、血管黏附分子-1(VCAM-1)水平,并取主动脉组织进行动脉粥样硬化斑块分析。结果 2组小鼠空腹血糖、甘油三酯(TG)、总胆固醇(TC)比较,差异无统计学意义(P>0.05);实验组高密度脂蛋白(HDC-C)高于对照组,差异具有统计学意义(P<0.05)。实验组动脉粥样硬化的斑块面积(7.55±1.87)%,较对照组(11.67±1.32)%明显减小,血清VCAM-1低于对照组,e NOS高于对照组,差异均具有统计学意义(P<0.05)。结论 DPP-4抑制剂西格列汀增加HDL水平,增加血清中e NOS含量,抑制VCAM-1的表达,进而抑制ApoE^(-/-)小鼠动脉粥样硬化进展。

Objective To investigate the effect of DPP-4 inhibitor sitagliptin on atherosclerosis and its mechanism. Methods Thirty male ApoE-/- mice were randomly divided into two groups：experimental group（ n = 15 ） and control group （n = 15 ）. The mice in the experi- mental group were fed with high-fat mixture of sitagliptin and the control group was fed with high fat. Collected blood in the eyeballs in order to analyze serum levels of blood lipids and blood glucose after 16 weeks of feeding, and detected serum nitric oxide synthase（eNOS） , vascular adhesion molecule-1 （ VCAM-1 ） with ELISA method. Collected aortic tissue in order to analyze atherosclerotic plaque. Results There was no significant difference in blood glucose, triglyceride and total cholesterol level between the two groups （ P 〉 0.05 ）. The serum high density lipo- protein in the experimental group was significantly higher than that in the control group（ P 〈 0.05 ）. The atherosclerotic plaque in the experi- mental group（7.55 ± 1.87 ）% , which was significantly smaller than that in the control group（ 11.67 ±1.32）%. The serum VCAM-1 in the experimental group was lower and the eNOS was higher than that in the control group（P 〈 0.05 ）. Conclusion DPP-4 sitagliptin can increase the expression of HDL and eNOS and inhibit the expression of VCAM-1 ,thereby inhibiting the progression of atherosclerosis in ApoE -/- mice.