非诺贝特对血管内皮细胞凝血酶诱导的内皮素-1表达的影响

Fenofibrate inhibits trombin-induced endothelin-1 expression in vascular endothelial cells

目的 :大量研究表明氧化体增殖物激活型受体α(PPARα)具有抗炎、抗动脉粥样硬化及扩张血管作用 ,本研究观察PPARα激动剂非诺贝特对牛主动脉内皮细胞 (BAECs)ET - 1表达的影响。方法 :制备 5 - 10代BAECs,用凝血酶及不同浓度非诺贝特 (10、5 0、10 0和 5 0 0 μmol/L)处理。采用放射免疫方法测定ET - 1含量 ,用RT -PCR法测定ET - 1mRNA表达。结果 :凝血酶明显增加ET - 1分泌 (2 2 4± 4 7vs对照 13 2± 1 6 )nmol/g蛋白质 ,P<0 0 1,非诺贝特 (10 0 μmol/L)对基础ET - 1分泌无影响。但以剂量依赖的方式抑制凝血酶诱导的ET - 1分泌 (2 2 3± 4 3、18 5± 2 8、13 4± 2 7和 11 7± 1 6 )nmol/g蛋白质 ,与对照组的 (2 5 6± 3 7)nmol/g蛋白质比较 ,均P <0 0 1。PT -PCR显示凝血酶明显增加ET - 1mRNA表达 ,此作用可为非诺贝特 (10 0 μmol/L)所抑制。结论 :PPARα激动剂非诺贝特抑制BAECs凝血酶诱导的ET - 1分泌及ET - 1mRNA水平 ,提示非诺贝特对凝血酶诱导的ET -

AIM: There has been accumulating evidence demonstrating that activators for peroxisome proliferator-activated receptor α (PPARα) have antiinflammatory, antiatherogenic, and vasodilatory actions. We investigated the effect of PPARα activator, fenofibrate, on trombin-induced endothelin-1 (ET-1) expression in cultured vascular endothelial cells. METHODS: Bovine aortic endothelial cells (BAECs) were treated with the PPARα activator, fenofibrate. The ET-1 concentrations were evaluated by radioimmunoassay. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the ET-1 mRNA expression. RESULTS: Thrombin(10U/L) induced ET-1 release in BAECs [(22.4±4.7) nmol/g protein vs control (13.2±1.6) nmol/g protein, P<0.01]. Fenofibrate (100 (μmol/L)) did not induce unstimulated ET-1 secretion, however, significantly inhibited the thrombin-induced ET-1 secretion in a dose-dependent manner at concentrations of 10, 50, 100 and 500 μmol/L [(22.3±4.3), (18.5±2.8), (13.4±2.7) and (11.7±1.6) nmol/g protein, compared with control (25.6±3.7) nmol/g protein, P<0.01]. Furthermore, thrombin significantly induced ET-1 mRNA expression, this induction was totally abolished in the presence of fenofibrate. These results indicate that fenofibrate inhibits thrombin-induced ET-1 production in BAECs at the gene expression level. CONCLUSION: PPARα activator, fenofibrate, inhibits thrombin-induced ET-1 production and mRNA expression in BAECs. [