KATP通道开放剂吡那地尔对兔肺动脉平滑肌细胞增殖的影响

目的: 研究吡那地尔(pinacidil, Pin) 对内皮素-1(ET-1) 诱导培养的兔肺动脉平滑肌细胞(PASMC)增殖的影响。方法: 内皮素-1 刺激培养兔PASMC 增殖模型;以氚-胸腺嘧啶核苷(³H]-TdR) 掺入法观察细胞增殖及脱氧核糖核苷酸(DNA) 合成;流式细胞仪技术检测兔PASMC 细胞周期。结果: 吡那地尔可剂量依赖性的抑制内皮素-1 所致的³H]-TdR 掺入量增多, 阻止兔PASMC 由静止期(G₀/G₁ 期) 进入DNA 合成期(S 期) 和有丝分裂期(G₂/M 期) 。ATP敏感性钾通道(K_ATP) 阻断剂格列本脲可拮抗吡那地尔对³H]-TdR 掺入的抑制作用。结论: 吡那地尔可能通过激活K_ATP通道抑制内皮素-1 诱导兔肺动脉平滑肌细胞的增殖, 可望用于治疗肺动脉高压时所致的肺动脉重构。

Effects of pinacidil on proliferation of cultured rabbit pulmonary arterial smooth muscle cells induced by endothelin-1

AIM: To explore the effects of pinacidil on the proliferation of rabbit pulmonary arterial smooth muscle cell (PASMC) induced by endothelin-1 in vitro. METHODS: The experimental model of proliferation of rabbit pulmonary arterial smooth muscle cell (PASMC) induced by endothelin-1 in vitro was established and ³H]-thymidine (³H]-TdR) incorporation and flow cytometric analysis (FCA) were used.RESULTS: Pinacidil markedly inhibited ³H]-TdR incorporation of PASMC induced by ET-1 and held back PASMC from static phase (G₀/G₁) to DNA synthesis (S) and mitotic phase (G₂/M) in the dose-dependent manner.Glibenclimide blocked the effects of pinacidil on ³H]-TdR incorporation. CONCLUSION: Pinacidil has an inhibitive effect on PASMC proliferation induced by ET-1 through activating ATP sensitive potassium (K_ATP) channels and K_ATP channels might play an important pathophysiologic role in the vascular remodeling.Pinacidil is a promising candidate in the treatment of pulmonary hypertension.