K_(ATP)通道开放剂对气道平滑肌细胞增殖表达及SOCS3/5免疫失衡的影响  

Research on the effect of the opening the ATP-sensitive K^+ channels opener on airway smooth muscle cells proliferation and immune imbalance SOCS3/5

作　　者：邓伊[1] 王志强[1] 

机构地区：[1]三峡大学医学院病理生理学系,宜昌443002

出　　处：《中国当代医药》2014年第29期4-7,共4页China Modern Medicine

基　　金：湖北省自然科学基金(2010CHB00201)

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。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-β1 and 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 5 groups,including normal ASMCs group,Ang II .ASMCs group,lymphocyte group,ASMCs and lymphocyte co-cultured group, Ang II .ASMCs and lymphocyte co-cultured group.Real-time PCR was used to measure the expression of SOCS3/5 mR- NA in Th cell.The level of TGF-β1 in serum were detected with ELISA.The changes after using the ATP sensitive K＋ channels opener Nicorandil was observed. Results Compared with ASMCs group,TGF-β1 was increased significantly in Ang II -ASMCs group （P〈0.01）;After treated with Nicorandil,every group had higher level of TGF-β1 comparing 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 Ang II .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-β1 by inhibiting the proliferation of ASMCs;SOCS3 and SOCS5 may be important targets for therapeutic strategies in asthma.

关 键 词：KATP通道开放剂 气道平滑肌细胞 细胞因子信号转导抑制因子 哮喘 

分 类 号：R965[医药卫生—药理学]