Y-27632对低氧性肺动脉收缩的作用  

Effect of Y-27632 on hypoxic pulmonary vasoconstriction

作　　者：刘蕾[1] 沈歆[1] 张志武[1] 肖雄[1] 李小强[1] 

机构地区：[1]第四军医大学药学院药理学教研室,西安710032

出　　处：《西北药学杂志》2015年第3期253-256,共4页Northwest Pharmaceutical Journal

基　　金：国家自然科学基金(No.81170107;No.30800433)

摘　　要：目的探讨Y-27632对低氧性肺动脉收缩的作用及其机制。方法建立小鼠低氧损伤模型;采用微血管张力实验测定肺动脉收缩力,WB检测TRPC6蛋白表达,离子影像技术测定平滑肌细胞全细胞钙变化。结果与对照组比较,CPA诱导低氧组肺动脉的收缩(加强到了167.9%±68.6%,*P<0.05;Y-27632可显著抑制这一变化(抑制率为47.3%±17.8%,#P<0.05);低氧可致肺动脉血管TRPC6蛋白表达显著增加(增加到154.8%±34.3%,*P<0.05),这一变化可被Y-27632显著降低(降低到134.2%±18.2%,#P<0.05);CPA诱导低氧组肺动脉平滑肌细胞[Ca2+]i显著升高(荧光比率升高到188.9%±46.6%,*P<0.05),此作用可被Y-27632显著抑制(荧光比率降低了46.7%±14.5%,#P<0.05)。结论 ROCK抑制剂Y-27632可通过调控TRPC6蛋白表达及其介导的[Ca2+]i变化,重要性地参与低氧性肺动脉收缩。Objective To investigate the effect of Y‐27632 on hypoxic pulmonary vasoconstriction and the potential mechanism . Methods Hypoxia‐induced injury model was made in mouse .CPA‐induced muscle contraction was detected by capillary tension experiment .To explore the expression of TRPC6 ,WB and immunofluorescence staining experiments were performed .Ca^2＋ was measured using a fluorescence imaging system .Results CPA‐induced muscle contraction was enhanced by 167 .9% ± 68 .6% in hypoxic pulmonary artery compared with control ,which was markedly inhibited by Y‐27632 （inhibition ratio was 47 .3% ± 17 .8% ,# P〈0 .05） .The expression of TRPC6 induced by hypoxia was markedly increased （to 154 .8% ± 34 .3% ,＊ P〈0 .05） . After treatment with Y‐27632 ,the expression of TRPC6 was significantly decreased compared with hypoxia mice （to 134 .2% ± 18 .2% ,# P〈0 .05） .Ca^2＋ influx in pulmonary artery smooth muscle cells elicited by store depletion using CPA were dramatically augmented in hypoxia group by 188 .9% ± 46 .6% in the ratio of 340 nm/380 nm（＊ P〈0 .05） .However ,Y‐27632 obviously at‐tenuated this change by 46 .7% ± 14 .5% （# P〈0 .05） .Conclusion Inhibition of ROCK by Y‐27632 can importantly take part in HPV via the regulation of TRPC6 expression in pulmonary artery ,which mediated extracellular Ca^2＋ influx .

关 键 词：钙离子 低氧性肺动脉收缩 经典瞬时受体电位通道蛋白 Y-27632 

分 类 号：R965[医药卫生—药理学]