吡那地尔对人肺动脉平滑肌细胞K_(ATP)通道蛋白及ERK1/2磷酸化的影响  

Effects of pinacidil on the expression of K_(ATP) channel protein and phosphorylation of ERK1/2 in primary cultured human pulmonary artery smooth muscle cells

作　　者：朱煜明[1] 解卫平[2] 王虹[2] 

机构地区：[1]常州市第一人民医院呼吸病科,213001 [2]南京医科大学第一附属医院呼吸病科

出　　处：《江苏医药》2011年第18期2122-2125,I0001,共5页Jiangsu Medical Journal

基　　金：江苏省自然科学基金(BK2006246)

摘　　要：目的探讨ATP敏感性钾(KATP)通道开放剂吡那地尔(Pin)对内皮素1(ET-1)诱导的人肺动脉平滑肌细胞(PASMCs)KATP通道蛋白表达及细胞外信号调节激酶1和2(ERK1/2)磷酸化的影响。方法体外培养人PASMCs,用ET-1诱导其增殖,应用Western blot方法评价Pin对ET-1诱导的人PASMCs KATP通道蛋白磺酰脲受体亚单位(SUR2B)和内向整流性孔区亚单位(Kir6.1)表达的影响以及ERK1/2的磷酸化作用。结果 ET-1显著下调SUR2B的表达,Pin呈浓度依赖性上调SUR2B表达;KATP通道拮抗剂格列本脲阻断Pin的作用,而Kir6.1的表达不受影响。ET-1呈时间依赖性促进人PASMCs ERK1/2磷酸化,10 min时最明显,Pin(10μmol/L)拮抗ET-1对ERK1/2磷酸化的影响,格列本脲逆转Pin的作用。结论 KATP通道开放剂Pin通过上调KATP通道蛋白的表达,抑制ET-1诱导的人PASMCs ERK1/2的磷酸化。Objective To explore the effects of pinacidil（Pin） on the expression of ATP-sensitive K＋（KATP） channel protein and phosphorylation of extracellular signal-regulated kinase1/2（ERK1/2） of primary cultured human pulmonary artery smooth muscle cells（PASMCs） induced by endothelin-1（ET-1）.Methods The experimental models of proliferation of primary cultured human PASMCs induced by ET-1 in vitro were established.The influence of Pin on the expression of SUR2B and Kir6.1,subunits of KATP channel protein of PASMCs,and the phosphorylation level of ERK1/2 induced by ET-1 were all detected by Western blot analysis.Results ET-1 downregulated the SUR2B subunit expression.Pin upregulated the SUR2B subunit expression in a concentration-dependent manner.Glibenclimide,a selective KATP channel blocker,abolished the effect of Pin.However,there was no significant difference in Kir6.1 subunit expression among the groups.ET-1 induced the phosphorylation of ERK1/2 with a peak response observed at 10 min in a time-dependent manner.Pin（10 μmol/L） inhibited ET-1-induced ERK1/2 phosphorylation.Glibenclimide antagonized the effect of Pin.Conclusion Pin inhibits the phosphorylation of ERK1/2 induced by ET-1 through upregulating the expression of KATP channel protein in primary cultured human PASMCs.

关 键 词：ATP敏感性钾通道 人肺动脉平滑肌细胞 细胞外信号调节激酶1和2 

分 类 号：R563[医药卫生—呼吸系统]