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

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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。

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关键词 ：大鼠, 尾加压素II, 转化生长因子-&beta, 1, 高肺血流性肺动脉高压

Abstract：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 pressure and 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.

Key words： rats urotensin II transforming growth factor-β1 high pulmonary blood flow pulpulmonary arterial hypertension

收稿日期: 2017-12-30

基金资助:温州市公益性科技计划项目（Y20140492）。

通讯作者: 吴蓉洲，教授，Email：wrz71@hotmail.com

作者简介: 张松跃（1980-），女，浙江温州人，主治医师，硕士。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2018/V48/I6/441

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