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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 investigate the effects of Pinacidil, a KATP channel opener, on the expression of KATP channel proteins in human pulmonary arterial smooth muscle cells (PASMCs) induced by endothelin-1 (ET-1) and the effects of extracellular signal-regulated kinases 1 and 2 (ERK1 / 2) phosphorylation. Methods Human PASMCs were cultured in vitro and induced by ET-1. Western blot was used to evaluate the effect of Pin on ET-1-induced KATP channel protein sulfonylurea subunit (SUR2B) and inward rectifying pore subunit Kir6.1) expression and the phosphorylation of ERK1 / 2. Results ET-1 significantly down-regulated SUR2B expression and Pin up-regulated SUR2B expression in a concentration-dependent manner. Glibenclamide, a KATP channel antagonist, blocked the effect of Pin, whereas Kir6.1 expression was not affected. ET-1 promoted phosphorylation of ERK1 / 2 in human PASMCs in a time-dependent manner, and Pin (10μmol / L) antagonized the effect of ET-1 on ERK1 / 2 phosphorylation at 10 min. Glibenclamide reversed the effect of Pin. Conclusions Pin, a KATP channel opener, inhibits ET-1-induced phosphorylation of ERK1 / 2 in human PASMCs by up-regulating KATP channel protein expression.