罗格列酮对动脉粥样硬化大鼠血清晚期糖基化终产物的影响及可能机制

目的:观察晚期糖基化终产物在动脉粥样硬化大鼠血清中的水平,以及应用胰岛素增敏剂罗格列酮对其的影响,并探讨其可能机制。方法:通过一次性维生素D3注射+高脂喂养法建立动脉粥样硬化模型。动物分组:A组:动脉粥样硬化模型组,B组:罗格列酮治疗组,C组:正常对照组,24周后处死全部大鼠,测定大鼠血清晚期糖基化终产物(AGE)、丙二醛(MDA)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、总胆固醇(TC)、甘油三脂(TG)水平。计算血浆致动脉硬化指数(AIP)。取主动脉全段,HE染色分析大鼠主动脉病变,PHOTOSHOP系统测定粥样斑块面积占内膜面积的百分比。免疫组化法观察主动脉丙二醛修饰低密度脂蛋白(MDA-LDL)的沉积。结果:大鼠血清AGE水平A组>B组>C组(P均<0.01)。MDA血清水平亦有A组>B组>C组(P值分别<0.05和0.01)。AIP数值A组>B组>C组(P均<0.01)。TC、LDL血清水平A组和B组均高于C组(P均<0.01),A组和B组之间无统计学差异。除C组外,其他两组大鼠主动脉均见粥样斑块形成,A组动脉粥样斑块面积/内膜面积百分比(38%±6%)高于B组(26%±8%)(P<0.05),A组粥样斑块病变部位MDA-PLDL的沉积面积较B组大(P<0.01,AGE与AIP值呈正相关(r=0.698,P<0.01),AGE与血清MDA呈正相关(r=0.514,P<0.05)。结论:血清AGE增高是动脉粥样硬化的危险因素之一。应用罗格列酮可以降低AGE水平,改善动脉损伤。AGE导致动脉粥样硬化的机制可能与增加氧化应激和增高血浆致动脉硬化指数有关。

Effects of Rosiglitazone on Advanced Glycation End Products in Atherosclerosis Rats

Objective: To investigate the effects of rosiglitazone on advanced glycation end (AGE) products in atherosclerosis rats. Methods: Experimental models of atherosclerosis of rats were established by injecting with a single dose of vitamin D3 and feeding with high fat diet. Wistar rats were randomly divided into control group, atherosclerosis group and rosiglitazone treatment group. After 12 weeks, all rats were killed and levels of AGE, MDA, HDL, LDL, TG and TC were measured respectively. Atherogenic index of plasma (AIP) was calculated. Arteriae aorta pathological changes were analyzed. Results: AIP and the serum levels of AGE and MD Awere significantly higher in atherosclerosis group than the other groups. TC and LDL were significantly lower in control group than the other groups. The relative plaque area was significantly increased in atherosclerosis group (38%±6%) than in rosiglitazone group (26%±8%). No plaque could be found in control group. Deposition of MDA-LDL in atherosclerotic lesions was down-regulated in rosiglitazone group when compared with artherosclerosis group. The serum level of AGE was directly correlated with AIP(r=0.698,P<0.01)or serum MDA concentration(r=0.514, P<0.05). Conclusion: High concentration of AGE is one of the risk factors of atherosclerosis. Rosiglitazone can depress the serum level of AGE and alleviate the lesions of artery. AGE accelerates the atheromatous plaque formation through induction of oxidative stress and increasing AIP.