目的：探讨电压依赖性钾离子通道Kv1．5对大鼠低氧高二氧化碳性肺动脉平滑肌细胞（ PASMCs）增殖、凋亡的影响及其与丝裂原激活蛋白激酶（ MAPK）信号通路的关系。方法：体外培养大鼠PASMCs，复制低氧高二氧化碳模型，随机分组如下：常氧组（ N组）；低氧高二氧化碳组（ HH组）；低氧高二氧化碳＋溶剂DMSO对照组（ HD组）；低氧高二氧化碳＋ERK1/2通路抑制剂U0126组（ HU组）；低氧高二氧化碳＋p38 MAPK通路抑制剂SB203580组（ HS组）；低氧高二氧化碳＋MAPK通路激动剂茴香霉素（ anisomycin ）组（ HA组）。采用CCK-8法检测细胞活性，蛋白免疫印迹法检测Kv1．5、增殖细胞核抗原（ PCNA）及Bax蛋白的表达水平。结果：与N组相比，HH组和HD组细胞活性增加（P＜0．01），PCNA蛋白表达上调，Kv1．5及Bax蛋白表达均明显降低（P＜0．01）， HH组和HD组间各指标变化均无显著差异（均P＞0．05）；较之HD组，HU组、HS组及HA组细胞活性降低（ P＜0．05或P＜0．01），PCNA蛋白表达下调，Kv1．5及Bax蛋白表达均明显增加，差异均显著（P＜0．01），其中以HA组各指标变化最明显。结论：钾离子通道Kv1．5对低氧高二氧化碳性大鼠PASMCs增殖、凋亡的调节可能与MAPK通路的激活有关。%AIM:To investigate the effects of voltage-dependent K +channel 1.5 (Kv1.5) on the proliferation and apoptosis of rat pulmonary artery smooth muscle cells (PASMCs) under hypoxia+hypercapnia condition and the relation-ship with mitogen-activated protein kinase(MAPK) signal pathway.METHODS:The PASMCs isolated from the male SD rat were cultured under hypoxia +hypercapnia condition, and randomly divided into normal group (N group), hypoxia+hyper-capnia group (HH group), hypoxia+hypercapnia+DMSO incubation group (HD group), hypoxia+hypercapnia +U0126 (an extracellular signal-regulated kinase 1/2 inhibitor) incubation group (HU group), hypoxia+hypercapnia+SB203580 (a p38 mitogen-activated protein kinase inhibitor ) incubation group (HS group), and hypoxia+hypercapnia+anisomycin (an agonist of MAPK) incubation group (HA group).Cell Counting Kit-8 was used to detect the cell viability.The protein expression of Kv1.5, PCNA and Bax was detected by Western blotting .RESULTS:Compared with N group , the cell via-bility and PCNA protein expression in HH group and HD group were significantly raised (P<0.01), but Kv1.5 and Bax proteins were significantly decreased (P<0.01).No difference between HH group and HD group was observed (P>0.05 ) .Compared with HD group , the cell viability and PCNA protein expression in HU group , HS group and HA group were decreased (P<0.05 or P<0.01), but Kv1.5 protein and Bax protein were raised (P<0.01), with the most significant changes in HA group .CONCLUSION:The regulation of Kv1.5 to the proliferation and apoptosis of PASMCs under hy-poxia+hypercapnia condition might have a relationship with the activation of MAPK signal pathway .
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