慢性低氧钙激活氯通道在大鼠肺动脉平滑肌细胞增殖中的作用

目的探讨慢性低氧时钙激活氯通道（ClCa）在大鼠肺动脉平滑肌细胞（PASMCs）增殖中的作用。方法将PASMCs分别置于常氧及慢性低氧下,采用形态学、流式细胞术、免疫细胞化学法,观察ClCa阻滞剂尼氟灭酸（NFA）和indaryloxyacetic acid（IAA-94）对PASMCs增殖的影响。结果慢性低氧：①PASMCs呈合成表型,而常氧为收缩表型,NFA和IAA-94干预后呈合成表型的PASMCs向收缩型转变;②S＋G2M期细胞所占比例增高,NFA和IAA-94干预后减低,且G0G1期细胞所占比例增加（P〈0.01）;③PCNA表达阳性率增高,NFA和IAA-94干预后降低（P〈0.01）;④c-fos和c-jun蛋白阳性染色A增高,NFA和IAA-94干预后降低（P〈0.01）。结论慢性低氧引起细胞表型改变,可促进细胞增殖,而抑制ClCa的活性可抑制细胞的增殖,提示ClCa参与了低氧PASMCs的增殖。

Effect of calcium-activated chloride channels on proliferation of pulmonary artery smooth muscle cells in rats under chronic hypoxic condition

Objective To investigate the effect of calcium-activated chloride（ClCa） channels on proliferation of pulmonary artery smooth muscle cells（PASMCs） in rats under chronic hypoxic condition.Methods The cultured PASMCs were under normoxic and chronic hypoxic conditions：The cells were observed by light and electron microscope;The cell cycles were observed by flow-cytometry;Immunocytochemistry staining was used to detect the expressions of PCNA,c-fos and c-jun of PASMCs.Results The PASMCs were contractile phenotype under normoxic condition and were synthetic phenotype under chronic hypoxic condition.After NFA and IAA-94,the situations were reversal;The number of S ＋ G2M PASMCs were significantly increased in chronic hypoxic condition;The NFA and IAA-94 were significantly decreased after intervention and the number of G0G1 PASMCs were significantly increased（P 0.01） ;In chronic hypoxic condition,the expression of proliferating cell nucleus antigen was significantly increased;The NFA and IAA-94 were significantly decreased（P 0.01） ;The expression A of c-fos and c-jun were significantly increased in chronic hypoxic condition;The NFA and IAA-94 were respectively significantly decreased（P 0.01）.Conclusion Hypoxic initiated the changes of PASMCs from contractile to synthetic phenotype could increase proliferation of PASMCs.NFA and IAA-94 could depress cell proliferation by blocking ClCa channels in hypoxic condition.These may play an important role in proliferation of PASMCs under chronic hypoxic condition.