【摘要】 目的研究ATP敏感性钾通道(KATP通道)开放剂对气道平滑肌细胞(ASMCs)增殖过程的影响,以及细胞因子信号转导抑制蛋白3/5(SOCS3/5)表达变化与转化生长因子-β1(TGF-β1)分泌释放水平的关系。方法体外构建增殖型ASMCs原代培养细胞模型,分为ASMCs组、AngⅡ·ASMCs组、淋巴细胞(L)组、ASMCs+L组和AngⅡ·ASMCs+L组。Real-time PCR检测细胞中SOCS3 mRNA及SOCS5 mRNA表达的差异;ELISA法检测上清液中TGF-β1的释放水平。观察KATP通道开放剂尼可地尔(NCR)干预的影响。结果与ASMCs组比较,AngⅡ·ASMCs组TGF-β1的表达水平明显升高(P<0.01);NCR作用于细胞后各组ASMCs表达TGF-β1与格列本脲(GLI)比较明显减少(P<0.05)。与ASMCs+L组比较,AngⅡ·ASMCs+L组SOCS3 mRNA表达增加,而SOCS5 mRNA表达减少(P<0.05)。NCR可以下调SOCS3的表达,上调SOCS5的表达。结论 KATP通道开放可以通过抑制ASMCs增殖而调控TGF-β1分泌表达;SOCS3和SOCS5可能是哮喘气道重塑的特异性免疫治疗中的重要靶点。更多还原

【Abstract】 Objective To explore the mechanisms of ATP sensitive K+channels opener affect on the progress of ASMCs proliferation,and the relationship of the change of TGF-β1and the suppressor of cytokines signaling 3/5(SOCS3/5).Methods The proliferative cell model of ASMCs were co-cultured in vitro with T lymphocyte,which were divided into 5groups,including normal ASMCs group,AngⅡ·ASMCs group,lymphocyte group,ASMCs and lymphocyte co-cultured group,AngⅡ·ASMCs and lymphocyte co-cultured group.Real-time PCR was used to measure the expression of SOCS3/5 mRNA in Th cell.The level of TGF-β1in serum were detected with ELISA.The changes after using the ATP sensitive K+channels opener Nicorandil was observed. Results Compared with ASMCs group,TGF-β1was increased significantly in AngⅡ·ASMCs group(P<0.01);After treated with Nicorandil,every group had higher level of TGF-β1comparing with Glibenclamide(P<0.05).Compared with ASMCs and lymphocyte co-cultured group,the expression of SOCS3 mRNA increased and the expression of SOCS5 mRNA decreased in the AngⅡ·ASMCs and lymphocyte group(P<0.05).Nicorandil could influence the expression of SOCS. Conclusion ATP sensitive K+channels opener may regulate the expression of TGF-β1by inhibiting the proliferation of ASMCs;SOCS3 and SOCS5 may be important targets for therapeutic strategies in asthma.更多还原