钙池操纵性钙通道在新型肺高压大鼠中的作用  

Enhanced store-operated Ca2 ＋ entry and canonical transient receptor potential expression in new rat model of pulmonary hypertension

作　　者：戴贻权[1] 刘晓如[2] 

机构地区：[1]福建医科大学附属第一医院血管外科,福州350004 [2]福建医科大学生物化学与分子生物学系福建医科大学心血管科学实验室

出　　处：《中华实验外科杂志》2015年第5期1081-1083,共3页Chinese Journal of Experimental Surgery

基　　金：2013年福建省卫生厅青年科研课题项目（2013-1-21）

摘　　要：目的 探讨规范性瞬时感受器电位通道1（TRPC1）蛋白-钙池操纵性钙通道（SOCC）在新型肺高压发病过程中的作用.方法 在左肺叶切除（PE）复合腹腔注射野百合碱（MCT）的肺高压大鼠模型中观察SOCC表达及功能变化.结果 与对照组（CON）比较,PE＋ MCT组TRPC1mRNA为其（3.40±1.59）倍（P＜0.05）;环匹阿尼酸（CPA）触发的肺动脉收缩由（16.6±1.5）％增加至（126.6±15.4）％（P＜0.01）,肺动脉平滑肌细胞的[Ca^2＋]i由（268±76） nmol/L增加至（1 832±867） nmol/L（P ＜0.01）;钆离子舒张效应由（36.9±3.7）％增加至（70.1±2.6）％（P＜0.05）.结论 PE＋ MCT上调了大鼠肺动脉TRPC1表达,增强了由TRPC1/SOCC介导的肺动脉平滑肌细胞的Ca^2＋内流和肺血管收缩,从而诱导大鼠产生肺高压,并进一步诱发肺血管及右心室重构.Objective To investigate the role of canonical transient receptor potential 1 （TRPC1）in pneumonectomy （PE） plus subcutaneous injection of monocrotaline （MCT）-induced pulmonary artery hypertension （PH） in rats.Methods SD rats underwent unilateral lobectomy,and 1 week later,rats were intraperitoneally injected with 2% MCT （50 mg/kg）.After 3 weeks,mean right ventricular pressure （mRVP） and right ventricular mass index （RVMI） were measured.The lung sections were stained by hematoxylin and eosin （HE） and observed under light microscope.Real-time reverse transcriptase-polymerase chain reaction（RT-qPCR） was performed to detect TRPC1 mRNA expression in rat pulmonary arteries （PAs）.Store-operated calcium channel （SOCC） agonist cyclopiazonic acid （CPA）-induced PAs contraction was measured by vascular ring tension analysis and the intracellular Ca^2＋ concentration （[Ca^2 ＋] i） of pulmonary artery smooth muscle cells （PASMCs） was monitored by Fluo3-AM assay.Meanwhile the effect of endothelin-1 （ET-1）-induced vasocontration,and the relaxation of gadolinium （Gd3 ＋） on ET-1-induced PAs contraction was measured.Results In comparison to the control group,rats developed severe PAH,and right ventricular hypertrophy in PE ＋ MCT group.The expression of TRPC1 mRNA in control group was more than 3 folds of that in PE ＋ MCT group.CPA-induced vasoconstriction was increased from （16.6 ± 1.5）% in control group to （126.6 ± 15.4）% in PE ＋ MCT group （n =8,P 〈 0.01）,and Ca^2 ＋ influx in PASMCs evoked by CPA was enhanced from （268 ± 76） nmol/L in control group to （1 832 ± 867） nmol/L in PE ＋ MCT group （n =8,P 〈 0.01）.Gd3 ＋-induced relaxation to Endothelin-1 vasoconstriction was also potentiated from （36.9 ± 3.7） % in control group to （70.1 ±2.6） % in PE ＋ MCT group （n =8,P 〈 0.05）.Conclusion PE ＋ MCT-induced PH is associated with increased TRPC1 expression and TRPC/SOCC-induced store operated Ca^2 ＋ entry.

关 键 词：钙离子 肺叶切除 野百合碱 

分 类 号：R544.1[医药卫生—心血管疾病]