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TRPC6介导肺动脉高压大鼠肺动脉张力和肺动脉平滑肌细胞Ca~(2+)浓度的升高
引用本文:张明芳,刘晓如,杨娜,林默君. TRPC6介导肺动脉高压大鼠肺动脉张力和肺动脉平滑肌细胞Ca~(2+)浓度的升高[J]. 生理学报, 2010, 0(1)
作者姓名:张明芳  刘晓如  杨娜  林默君
作者单位:福建医科大学基础医学院生理学与病理生理学系;
基金项目:supported by the National Natural Science Foundation of China(No.30670772); the Natural Science Foundation of Fujian Province(No.C0620002); the Key Program of Scientific Research of Fujian Medical University(No.09ZD010)
摘    要:经典瞬时感受器电位通道6(transient receptor potential channel6,TRPC6)蛋白是受体操纵性Ca2+通道(ROCC)的分子基础。本文旨在研究TRPC6/ROCC在野百合碱(monocrotaline,MCT)诱发的肺动脉高压大鼠模型中的作用。Sprague-Dawley大鼠随机分为正常对照组(CON组)和MCT组,CON组正常饲养三周,而MCT组按60mg/kg剂量一次性腹腔注射2%MCT,建立MCT诱导的慢性肺动脉高压大鼠模型。通过测定右心室收缩压(RVSP)和右心室重量指数(RVMI)、HE染色观察肺动脉血管形态,分析肺动脉结构重建。半定量RT-PCR和Western blot检测大鼠肺动脉TRPC6 mRNA和蛋白表达水平。血管张力实验中用可特异性激活ROCC、可透膜的DAG拟似物1-oleoyl-2-acetyl-sn-glycerol(OAG)检测大鼠离体肺动脉环的收缩效应。用荧光探针Fluo3-AM测定OAG诱导大鼠肺动脉平滑肌细胞(PASMCs)胞浆游离Ca2+浓度([Ca2+]i)。结果显示,与CON组相比,MCT组的RVSP、RVMI均明显增高(P0.01);形态学观察可见肺小动脉平滑肌层明显增厚,管腔减小;TRPC6的mRNA和蛋白质表达无明显变化。在CON组,OAG几乎不引起肺动脉环收缩,而在MCT组,肺动脉环的收缩反应显著增强,差别有显著性意义(P0.01)。相比较于CON组,MCT也可使OAG触发的PASMCs[Ca2+]i增量值显著升高(P0.05)。上述结果提示,MCT预处理对肺动脉TRPC6mRNA和蛋白质水平的表达无显著增强效应,但可促进TRPC6/ROCC介导的PASMCsCa2+内流和肺动脉张力升高,诱导大鼠产生肺动脉高压,并进一步诱发肺血管及右心室重构。

关 键 词:经典瞬时感受器电位  钙离子  受体操纵性Ca2+通道  野百合碱  

TRPC6 mediates the enhancements of pulmonary arterial tone and intracellular Ca~(2+) concentration of pulmonary arterial smooth muscle cells in pulmonary hypertension rats
ZHANG Ming-Fang,LIU Xiao-Ru,YANG Na,LIN Mo-Jun. TRPC6 mediates the enhancements of pulmonary arterial tone and intracellular Ca~(2+) concentration of pulmonary arterial smooth muscle cells in pulmonary hypertension rats[J]. Acta Physiologica Sinica, 2010, 0(1)
Authors:ZHANG Ming-Fang  LIU Xiao-Ru  YANG Na  LIN Mo-Jun
Affiliation:ZHANG Ming-Fang,LIU Xiao-Ru,YANG Na,LIN Mo-Jun Department of Physiology , Pathophysiology,Fujian Medical University,Fuzhou 350004,China
Abstract:Pulmonary arterial hypertension is associated with profound vascular remodeling and alterations in Ca2+ homeostasis in pulmonary arterial smooth muscle cells (PASMCs).Recent studies show that canonical transient receptor potential channel 6 (TRPC6) genes,which encode receptor-operated cation channels (ROCC) in PASMCs,play an important role in Ca2+ regulation and cell proliferation.The aim of the present study was to investigate the role of TRPC6 in monocrotaline (MCT)-induced pulmonary artery hypertension.S...
Keywords:pulmonary arterial hypertension  transient receptor potential channels  Ca2+  receptor-operated Ca2+ channel  monocrotaline  
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