非诺贝特对血管钙化的影响及机制研究

Effect and mechanism of fenofibrate on vascular calcification model rats

目的在大鼠血管钙化模型上,探讨过氧化物酶体增殖物激活受体α(peroxisome proliferator activated re-ceptorα,PPARα)激动剂非诺贝特对血管钙化的影响及其可能的作用机制。方法实验动物按随机数字表法分正常组、钙化组及钙化+非诺贝特组,每组10只。钙化组采用维生素D3和尼古丁诱导大鼠血管钙化模型,钙化+非诺贝特组于造模后第2天开始,非诺贝特灌胃[30 mg/(kg·d)]。采用Von Kossa染色检测血管钙化程度,采用钙离子测试盒、碱性磷酸酶(alkaline phosphatase,ALP)试剂盒测定大鼠主动脉钙浓度和ALP活性,采用Beckman Coulter AU5800仪器检测血清三酰甘油(triacylglycerol,TG)浓度,采用放射免疫法检测大鼠血清单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)浓度,采用免疫组织化学法检测主动脉MCP-1受体表达。结果 Von Kossa染色可见血管钙化模型大鼠主动脉有大量黑色颗粒沉淀,钙化组血管钙浓度、ALP活性高于正常组,差异有统计学意义(P<0.01);同时,与正常组比较,钙化组血清MCP-1浓度和主动脉组织MCP-1受体表达明显上调(P<0.01)。用非诺贝特干预后,血管钙化程度减轻(P<0.01),同时血清MCP-1及其受体的表达下调,与钙化组比较差异有统计学意义(P<0.01)。3组动物血清TG浓度比较,差异无统计学意义(P>0.05)。结论 PPARα激动剂非诺贝特可抑制血管钙化,可能通过下调MCP-1表达和ALP活性抑制血管钙化的发生、发展过程。

Objectives To study the effect and possible mechanism of peroxisome proliferator activated receptorα(PPARα)agonist fenofibrate in rats with vascular calcification.Methods Male SD rats were randomly divided intonormal group,calcification group and calcification plus fenofibrate group(all n=10per group).Vascular calcificationwas induced by vitamin D3plus nicotine.The next day after calcification induction,rats in fenofibrate group weregavaged with fenofibrate[30mg/(kg·d)]for four weeks.Vascular calcification was confirmed by Von Kossa staining.Calcium concentration and alkaline phosphatases(ALP)activity were detected by calcium assay kit and ALP detectionkit respectively.Triglyceride(TG)concentration in serum was detected by Beckman Coulter AU5800.Monocytechemoattractant protein-1(MCP-1)concentration in serum was determined by radioimmunoassay,and the expressionsof corresponding receptors were determined by immunohistochemistry.Results Von Kossa staining showed that therewere mass black granules deposited in aortic wall of the vascular calcified rats.Calcium concentration and ALP activityin calcified group significantly increased than those in control group(P<0.01and P<0.01).Meanwhile,MCP-1con?centration in serum and expression of corresponding receptor in calcified group were significantly higher than those incontrol group(P<0.01).In addition,fenofibrate diet could reduce vascular calcium concentration,ALP activity andMCP-1concentration.There were no significant differences in serum concentrations of TG among these groups(P>0.05).Conclusions Ours results indicated that PPARαagonist(fenofibrate)significantly protects the aorta against calcification partly through reducing MCP-1concentration and ALP activity.