14,15-EET通过TRPV4-SK_(Ca)复合物调节气管平滑肌收缩机制研究  

14,15-epoxyeicosatrienoic acid regulates airway smooth muscle contraction through TRPV4-SK_(Ca) signal complex

作　　者：张洁[1] 沈兵[1] 桑大成 杜鹃[1] 丁圣刚[2] 

机构地区：[1]安徽医科大学基础医学院生理学教研室,合肥230032 [2]安徽医科大学第一附属医院儿科,合肥230022

出　　处：《安徽医科大学学报》2015年第5期565-568,共4页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81371284)

摘　　要：目的探讨花生四烯酸细胞色素P450(CYP)表氧化酶代谢产物14,15-环氧化二十碳三烯酸(14,15-EET)对小鼠气管平滑肌收缩功能的影响及其机制。方法采用离体气管实验,通过运用特异性钙激活钾通道阻断剂和瞬时受体电位离子通道4(TRPV4)通道阻断剂,观察14,15-EET对卡巴胆碱引起的小鼠气管收缩的影响;采用免疫共沉淀实验检测TRPV4通道蛋白与小电导钙激活钾通道(SKCa)蛋白在小鼠气管平滑肌组织中的相互作用。结果与对照组相比,300 nmol/L 14,15-EET预处理小鼠气管后,卡巴胆碱引起的收缩显著减弱;大、中电导钙激活钾通道阻断剂Ib TX和TRAM34没有显著影响14,15-EET对卡巴胆碱引起的小鼠气管收缩的抑制效应;而SKCa阻断剂Apamin和TRPV4通道阻断剂RN-1734都分别显著阻断了14,15-EET对卡巴胆碱引起的小鼠气管收缩的抑制作用。免疫共沉淀结果显示TRPV4通道蛋白和SKCa通道蛋白可以彼此相互共沉淀。结论在小鼠气管平滑肌中,14,15-EET通过TPRV4-SKCa钙信号复合物调节气管平滑肌的收缩。Objective To provide a mechanistic insight into how 14,15-epoxyeicosatrienoic acid （14,15-EET） which is a product of cytochrome P450 epoxygenase regulates mouse airway smooth muscle contraction. Methods Isolated mouse tracheal tension was measured in vitro. Mouse tracheal rings were treated by Ca2 ＋ -activated K ＋channel blockers or transient receptor potential vanilloid 4 （TRPV4） channel blocker. The changes of relaxation caused by 14,15-EET in tracheal rings were recorded after the tracheal rings were contracted by carbachol in con-centration-dependent fashion. Co-immunoprecipitation was used to examine the physical interaction between TRPV4 and SKCa in airway smooth muscle. Results Tracheal tension measurement showed that compared with the control group, carbachol-induced contraction in 300 nmol/ L 14,15-EET pretreatment group was significantly reduced. BK-Ca and IKCa blockers did not affect the effect of 14,15-EET on carbachol-induced tracheal contraction. However, SKCa and TRPV4 blockers notably inhibited the effect of 14,15-EET on carbachol-induced tracheal contraction, re-spectively. Conclusion 14,15-EET regulates airway smooth muscle contraction via TRPV4-SKCa signal complex.

关 键 词：钙激活钾通道 瞬时受体电位离子通道4 14 15- EET 气管平滑肌 

分 类 号：Q412[生物学—生理学]