摘要
目的从组织功能及细胞分子水平研究电压门控型钾通道(Kv通道)亚型在15-羟化二十碳四烯酸(15-HETE)致大鼠肺动脉收缩过程中的作用。方法采用组织浴槽血管环法,使用Kv通道阻断剂,确定受15-HETE调控大鼠肺动脉平滑肌细胞(PASMCs)膜上Kv亚型;使用RT-PCR和W estern b lotting技术观察受15-HETE调控PASMCs膜上Kv亚型。结果阻断Kv1.1,Kv1.2,Kv1.3和Kv1.6通道并不影响15-HETE诱导肺动脉血管收缩;15-HETE不影响PASMCs膜上Kv1.1和Kv1.2通道蛋白质表达;15-HETE下调PASMCs膜上Kv1.5和Kv2.1通道mRNA和蛋白质表达。结论缺氧可能是通过15-HETE这一介导因子抑制Kv1.5和Kv2.1通道,减少PASMCs膜上功能性Kv1.5和Kv2.1通道数量,导致PASMCs收缩。
Aim To observe the effect of subtypes of Kv channels in rat pulmonary artery smooth muscle cells （PASMCs） on the process of pulmonary vasoconstriction induced by 15-HETE. Methods In the present study, ring of rabbit PA with specific Kv channel blockers were employed to functionally identify certain channel subtypes that took part in the process of 15-HETE induced pulmonary vasoconstriction; RT-PCR and Western blotting analysis were also used to measure the expression of subtypes of Kv in PASMCs exposed to 15-HETE, chronic hypoxia. Results Blocking of Kvl.1, Kvl.2, Kvl.3 and Kvl.6 channels did not affect 15-HETE induced vasoconstriction in normoxic rats; 15-HETE did not affect expression of Kvl.1 and Kvl.2 channels; 15-HETE significantly downregulated the expression of mRNA and protein of Kvl.5 and Kv2.1 in rat PASMCs. Conclusion The results suggested that hypoxia may block Kvl.5 and Kv2.1 channels via 15-HETE mediated mechanism, leading to decrease numbers of functional Kv1.5 and Kv2.1 channels in PASMCs, leading to PA vasoconstriction.
出处
《药学学报》
CAS
CSCD
北大核心
2006年第5期412-417,共6页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(30370578
30470752)
黑龙江省教育厅海外学人研究重点资助项目(1053HZ004).
关键词
缺氧肺动脉收缩
电压门控性K+通道亚型
15-羟化二十碳四烯酸
肺动脉平滑肌细胞
hypoxic pulmonary vasoconstriction
voltage-gated potassium channel subtypes
15-hydroeicosatetraenoic acid
pulmonary artery smooth muscle cells
