内皮素-1诱导大鼠血管平滑肌细胞产生C-反应蛋白的作用

摘要

目的 观察内皮素1(ET-1)诱导血管平滑肌细胞(VSMCs)产生C-反应蛋白(CRP)的作用及其机制.方法 培养大鼠VSMCs,以不同浓度ET-1刺激VSMCs,并用ETA拮抗剂BQ123、抗氧化剂PDTC、p38MAPK抑制剂SB203580及ETB阻断剂BQ788进行干预,免疫细胞化学法及半定量逆转录聚合酶链反应(RT-PCR)法分别测定不同浓度及不同干预因素下VSMCs中CRP蛋白及mRNA的表达.结果 ET-1能刺激VSMCs CRP蛋白及mRNA的表达增强,其效应呈浓度依赖性；BQ123、PDTC及SB203580能明显减少ET-1诱导的大鼠VSMCs CRP蛋白及mRNA的表达,而BQ788对此作用无明显影响.结论 ET-1通过ETA、活性氧(ROS)、p38MAPK诱导大鼠VSMCs产生CRP.%To observe the effect of endothelin-1 (ET-1) on C-reactive protein (CRP) generation in rat vascular smooth muscle cells (VSMCs) and the primary mechanisms. Methods Rat VSMCs were cultured. CRP protein expression stimulated with ET-1 was examined with the immunocytochcmical method, and CRP mRNA expression was identified with the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Results ET-1 stimulated CRP generation in VSMCs at both protein and mRNA levels in a dose-dependent manner. ETA receptor antagonist BO123, but not ETB receptor antagonist BQ788, inhibited ET-1-stimulated mRNA and protein expressions of CRP in VSMCs. In addition, antioxidant pyrrolidine dithiocarbamate and p38MAPK inhibitor SB203580 reduced ET-1-induced mRNA and protein expressions of CRP. Conclusion ET-1 induces CPR production in rat VSMCs via ETA receptor and subsequent ROS and MAPK signal pathway.