尾加压素Ⅱ受体拮抗剂对高肺血流性肺动脉高压大鼠肺组织TGF-β1表达的影响  

The regulation of urotensin-Ⅱ on the expressions of TGF-β1 in rat model of high pulmonary blood flow pulmonary arterial hypertension

作　　者：张松跃[1] 任跃[1] 何跃娥[1] 李皓[1] 吴蓉洲[1] ZHANG Songyue;REN Yue;HE Yuee;LI Hao;WU Rongzhou(Children＇s Heart Center,Institute of Cardiovascular Development and Translational Medicine,the Second Affiliated Hospital ＆ Yuying Children＇s Hospital,Wenzhou Medical University,Wenzhou,32502)

机构地区：[1]温州医科大学附属第二医院育英儿童医院儿童心脏中心温州医科大学心脏发育与转化医学研究所,浙江温州325027

出　　处：《温州医科大学学报》2018年第6期441-445,共5页Journal of Wenzhou Medical University

基　　金：温州市公益性科技计划项目(Y20140492)

摘　　要：目的:研究尾加压素-Ⅱ(UⅡ)受体拮抗剂在大鼠高肺血流性肺动脉高压(PAH)模型中对转化生长因子β1(TGF-β1)表达的影响。方法:雄性SD大鼠60只随机均分为PAH组(S组)、假手术组(C组)、UⅡ抑制组(M组,给予UⅡ受体拮抗剂帕洛舒仑),每组20只。S组和M组行外科分流术建立PAH模型。造模后4、8、12周,每组取5只大鼠测右心室压力,于第12周留取肺组织标本,Western blot测肺组织中UⅡ和TGF-β1蛋白的表达;RT-PCR检测肺组织中TGF-β1 mRNA表达。多组间比较采用单因素方差分析,相关性采用Pearson相关分析。结果:3组肺动脉压力比较:和C组相比,S组大鼠肺动脉压力显著升高(P<0.05),M组较S组显著降低(P<0.05)。造模后第12周,和C组相比,S组大鼠肺组织中UⅡ蛋白表达量显著升高(P<0.05),M组较S组均显著降低(P<0.05)。造模后第12周,和C组相比,S组大鼠肺组织中TGF-β1 mRNA及蛋白表达量均显著升高(P<0.05),M组较S组均显著降低(P<0.05)。UⅡ蛋白表达量与肺动脉压力、TGF-β1 mRNA及蛋白表达量均呈正相关(r=0.987、0.979、0.966,P<0.05)。结论:UⅡ受体拮抗剂帕洛舒仑可能通过下调TGF-β1表达而缓解大鼠高肺血流性PAH形成。Objective： To explore the impact of urotensin-Ⅱ（UⅡ） on the expressions of transforming growth factor β1（TGF-β1） in rat model of pulmonary arterial hypertension triggered by high pulmonary blood flow. Methods： Sixty male SD rats were included and randomly divided into pulmonary hypertension model group（Group S, n=20）, sham group（Group C, n=20）, urotensin Ⅱ inhibitor group（Group M, n=20）. The pulmonary hypertension model was established after surgical connection of the common carotid artery and jugular vein in rats. Four weeks, eight weeks and twelve weeks later, 5 rats were selected from each group to measure the right ventricular pressure. Twelve weeks later, 5 rats from each group were sacrificed to obtain specimens of lung tissue. Western blot was used to detect the expression of UⅡ and TGF-β1 protein in lung tissue. The content of TGF-β1 mRNA was detected via RT-PCR. One-way analysis of variance and Pearson correlation analysis were used to analyze the data. Results： For the pulmonary artery pressure, Group S reached a higher level compared with Group C（P〈0.05）, and the level of Group M was significantly decreased when compared with Group S（P〈0.05）. Twelve weeks later, the content of UⅡ protein in Group S was remarkably increased（P〈0.05） while in Group M was relatively decreased（P〈0.05） compared with Group C. Twelve weeks later, the expression of both TGF-β1 mRNA and protein in Group S was higher than Group C（P〈0.05）, but in Group M it were significantly decreased（P〈0.05）. The expression of UⅡ protein was positively associated with pulmonary artery pressureand TGF-β1 mRNA and protein expression. Conclusion： The down-regulation of UⅡ reduces the expression of TGF-β1, which may ultimately alleviate the pulmonary hypertension in the rat model.

关 键 词：大鼠 尾加压素Ⅱ 转化生长因子-Β1 高肺血流性肺动脉高压 

分 类 号：R56[医药卫生—呼吸系统]