Kv1.5对大鼠低氧高二氧化碳性PASMCs增殖、凋亡的影响及与MAPK通路的关系  

Effects of Kv1. 5 on proliferation and apoptosis of rat PASMCs under hypoxia + hypercapnia condition and relationship with MAPK pathway

作　　者：马迎春[1] 郑梦晓 黄林静[1] 王园园[2] 应磊[1,3] 王万铁[1,3] 

机构地区：[1]温州医科大学基础医学院病理生理学教研室,浙江温州325035 [2]浙江省立同德医院病理科,浙江杭州310012 [3]温州医科大学缺血/再灌注损伤研究所,浙江温州325035

出　　处：《中国病理生理杂志》2014年第9期1645-1650,共6页Chinese Journal of Pathophysiology

基　　金：卫生部科学研究基金-浙江省医药卫生重大科技项目(No.WKJ2009-2-030);浙江省中医药重点学科建设计划项目(No.2012-XK-A28)

摘　　要：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 relationship 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 ＋ hypercapnia 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 viability 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 hypoxia ＋ hypercapnia condition might have a relationship with the activation of MAPK signal pathway.

关 键 词：Kv1.5钾通道 丝裂原激活蛋白激酶 肺动脉平滑肌细胞 细胞增殖 细胞凋亡 

分 类 号：R363[医药卫生—病理学]