细胞因子信号转导抑制因子3抑制血小板衍生生长因子-BB诱导的血管平滑肌细胞炎症反应的作用及其机制  

Suppressor of cytokine Signaling3 inhibits platelet derived growth factor-BB-mediated vascular smooth muscle cell inflammation

作　　者：刘金平[1] 向水[1] 董念国[1] 史嘉玮[1] 孟庆良[2] 肖勇[2] 

机构地区：[1]华中科技大学同济医学院附属协和医院心血管外科,武汉430022 [2]华中科技大学同济医学院附属协和医院胃肠外科,武汉430022

出　　处：《中华实验外科杂志》2012年第4期581-584,共4页Chinese Journal of Experimental Surgery

摘　　要：目的探讨细胞因子信号转导抑制因子3（SOCS3）抑制血管平滑肌细胞炎症反应的作用及机制。方法用携带大鼠SOCS3基因的腺病毒（pYrAd—rSOCS3）转染血小板衍生生长因子-BB（PDGF—BB）刺激的大鼠动脉血管平滑肌细胞。实时定量聚合酶链反应（Realtime-PCR）检测SOCS3、白细胞介素（IL）-18、IL-6、肿瘤坏死因子（TNF）-α、单核细胞趋化蛋白-1（MCP-1）及细胞间黏附分子-1（ICAM-1）mRNA表达。Westernb lot检测SOCS3、信号转导及转录激活因子3（STAT3）、P-STAT3、IL-1B、IL-6、TNF-α、MCP-1及ICAM-1的的蛋白表达。结果PDGF-BB刺激血管平滑肌细胞24h后，SOCS3、STAT3、P—STA33、IL-1B、IL-6、TNF-α、MCP-1及ICAM-1表达均上调；pYrAd—rSOCS3转染血管平滑肌细胞后再用PDGF—BB刺激，其SOCS3表达进一步上调，但STA33、P—STAT3、IL-18、IL-6、TNF-α、MCP-1及ICAM-1表达明显下调。结论上调血管平滑肌细胞SOCS3表达通过负反馈调节酪氨酸蛋白激酶（JAK）-STAT3信号通路，抑制STAT3的激活及磷酸化而下调炎性细胞因子表达。Objective To investigate the inhibitory effect of suppressor of cytokine signaling3 （SOCS3） on the pro-inflammation of platelet-derived growth faetor-BB （PDGF-BB）-induced vascular smooth muscle cells （VSMCs）. Methods The recombinant adenovirns vector containing rat SOCS3 gene was transfected into VSMCs induced by PDGF-BB. After 24 h, real-time reverse transcription polymerase chain reaction （RT-PCR） and Western blotting were used to analyse the mRNA and protein expression of SOCS3, signal transducer and activators of transcription 3 （STAT3） （only by Western blotting）, P-STAT3 （ only by Western blotting） , interleukin （IL） -1β, IL-6, tumor necrosis factor （TNF） -α, monocyte che-moattractant protein （MCP）-1 and intercellular adhesion molecule-1 （ICAM-1）. Results The expression levels of SOCS3 mRNA and protein, STAT3 protein, P-STAT3 protein, IL-1β, IL-6, TNF-α, MCP-1 and ICAM-1 were significantly up-regulated in VSMCs induced by PDGF-BB. However, after VSMCs were transfected with pYrAd-rSOCS3 and treated with PDGF-BB, the expression of SOCS3 mRNA and protein was further up-regulated, and that of STAT3 protein, P-STAT3 protein, IL-1β, IL-6, TNF-α, MCP-1 and ICAM-1 was significantly down-regulated. Conclusion In VSMCs, up-regulated SOCS3 may inhibit pro- inflammatory effect of VSMCs by blocking STAT3 activation and phosphorylation through negatively regulating JAK-STAT3 signaling pathway. These results can provide a novel idea for clinical treatment of vascular proliferation diseases.

关 键 词：细胞因子信号转导抑制因子3 炎性细胞因子 血管平滑肌细胞 冠心病 

分 类 号：R285.5[医药卫生—中药学]