肺动脉高压对右心重构及右心室AT_1R、TGF-β1、ERK1/2蛋白表达的实验研究  

The expression of AT_1R,TGF-β1 and ERK1 /2 on pulmonary arterial hypertension related right ventricular remodeling in monocreotaline-induced rats

作　　者：郭雯[1] 马涵英[1] 赵铁夫[2] 吴思婧 侯微微 李银花[1] 董芳[1] 赵迎新[1] 周玉杰[1] 张维君[1] 

机构地区：[1]首都医科大学附属北京安贞医院-北京市心肺血管疾病研究所心内科,北京100029 [2]首都医科大学附属北京安贞医院-北京市心肺血管疾病研究所心外科,北京100029 [3]首都医科大学附属北京安贞医院-北京市心肺血管疾病研究所呼吸科,北京100029

出　　处：《心肺血管病杂志》2014年第2期296-299,共4页Journal of Cardiovascular and Pulmonary Diseases

基　　金：国家自然科学基金青年科学基金项目(No.81200179);北京市优秀人才资助计划(No.2011D003034000015);教育部高等学校博士学科点专项科研基金(No.20111107120021)

摘　　要：目的：探讨肺动脉高压（pulmonary arterial hypertension,PAH）对大鼠右心重构及右心室AT1R,TGF-β1及ERK1/2蛋白的表达.方法：选取体质量250～ 260g的健康雄性SD大鼠12只,随机分为：对照组（n=6）、PAH右心重构组（n=6）.对照组和PAH右心重构组分别予以0.9％氯化钠液和野百合碱（MCT） 60 mg/kg单次注射于大鼠颈背部皮下,饲养6w建立模型.应用超声生物显微镜测定其右心室前壁厚度（RVAWd）及右心室射血分数（RVEF）,应用右心导管测定肺动脉平均压（mPAP）.处死后分别称量右心室（RV）和左心室＋室间隔（LV＋ SP）质量,计算右心室肥厚指数（RVHI）.天狼猩红染色计算心肌组织胶原容积分数（CVF）.应用Western blot测定右心室AT1R,TGF-β1,ERK1/2蛋白表达.结果：与对照组相比,野百合碱诱导6w后,PAH右心重构组的RVAWd、mPAP、RVHI及CVF均高于对照组,差异有统计学意义,分别为RVHI[（25.01±1.20） vs.（40.57±4.17）％],mPAP[（16.56±1.98） vs.（29.46±2.47）mmHg],RVAWd[（0.65 ±0.09）vs.（1.17 ±0.08）mm],RVEF [（54.15±4.60）vs.（62.63 ±9.54）％],均为P＜0.01;PAH右心重构组右心室心肌组织AT1R、TGF-β1及ERK1/2蛋白表达显著高于对照组（均为P＜0.05）.结论：肺动脉高压对大鼠右心重构及右心室AT1R、TGF-β1及ERK1/2蛋白表达显著上调.Objective：To observe the potential mechanism on pulmonary hypertension related right ventricle Remodeling in monocrotaline （MCT）-induced rats.Methods：12 male Sprague-Dawley rats were randomly divided into 2 groups：control group and pulmonary arterial hypertension（PAH） group （induced by injection of MCT 60mg/kg）.Mter 6 weeks,all survival rats were detected by echocardiography to observe the RV anterior wall diameter （RVAWd） and RV eject fraction （RVEF）.All survival rats were measured by right catheterization to observe mean pulmonary artery pressure （mPAP）.Right ventricle hypertrophy index （RVHI） were weighted.Collagen volume fraction （CVF） were detected.Expressions of AT1 R,TGF-β1 and ERK1/2 protein of right ventricles tissue were determined by western blot.Results：Compared with the control group,RVAWd,mPAP and RVWI significantly increased in PAH group,RVHI[（25.01 ± 1.20）％ vs.（40.57 ± 4.17） ％],mPAP[（16.56 ± 1.98） vs.（29.46 ± 2.47） mmHg],RVAWd [（0.65 ± 0.09） vs.（1.17 ± 0.08） mm],RVEF [（54.15 ± 4.60） vs.（62.63 ± 9.54） ％],P ＜ 0.01 separately.CVF in PAH group was significant higher than that in control group （P ＜0.01）.Compared with control group,AT1R,TGF-β1 and ERK1/2 protein expression markedly increased （P ＜ 0.05） in PAH group.Conclusion：In MCT-induced pulmonary hypertension related right ventricular remodeling rats,AT1 R,TGF-β1 and ERK1/2 protein expression of right ventricles were up-regulated.

关 键 词：肺动脉高压 右心重构 AT1R TGF-Β1 ERK1 2 

分 类 号：R54[医药卫生—心血管疾病]