高血流性肺动脉高压大鼠肺组织中TGF-β1和CTGF的动态变化及意义  

Changes of TGF-β1 and CTGF in rats with increased blood flow-induced pulmonary artery hypertension

作　　者：朱蓉[1] 贺亮[1] 徐军美 张燕玲[1] 胡永斌[2] 

机构地区：[1]中南大学湘雅二医院麻醉科,麻醉医学研究所,长沙410011 [2]中南大学湘雅医学院病理学系,长沙410013

出　　处：《中南大学学报（医学版）》2012年第10期1013-1020,共8页Journal of Central South University ：Medical Science

基　　金：湖南省自然科学基金(11JJ6075)~~

摘　　要：目的:观察转化生长因子-β1(TGF-β1)与结缔组织生长因子(CTGF)在高血流性肺动脉高压大鼠肺组织的动态表达变化,探讨TGF-β1和CTGF在高血流性肺动脉高压过程中的作用。方法:50只成年雄性SD大鼠随机分成假手术组(S组)、右肺切除1周组(PE1组)、2周组(PE2组)、4周组(PE4组)和6周组(PE6组),每组10只。测量各组大鼠平均肺动脉压(mPAP)、右室肥大指数(RVHI)和血管形态学指标;免疫组织化学染色和Western印迹检测肺组织TGF-β1和CTGF蛋白表达;RT-PCR检测TGF-β1和CTGF mRNA的表达。结果:与S组比较,右肺切除各时间组大鼠mPAP和RVHI均显著升高(P<0.05),PE1和PE 2组肌型动脉(MA)和部分肌型动脉(PMA)占肺中小血管总数的百分比[(MA+PMA)%]、MA的相对中膜厚度(RMT)和相对中膜面积(RMA)与S组比较无明显差异,PE4和PE6组(MA+PMA)%、RMT及RMA明显增高(P<0.05);免疫组织化学染色显示,右肺切除各时间组大鼠TGF-β1和CTGF较S组分布广泛,表达增强。Western印迹结果表明,与S组比较,右肺切除各时间组TGF-β1蛋白均显著上升(P<0.01),峰值出现在PE2组;CTGF蛋白在PE1组和PE2组较S组升高,但差异无统计学意义,PE4组和PE6组较S组明显增高(P<0.05)。与S组比较,右肺切除各时间组TGF-β1mRNA表达均显著升高(P<0.01),PE2组达峰值,PE4组和PE6组维持在高水平。PE1组CTGF mRNA增高不明显,PE2组、PE4组和PE6组明显上升(P<0.01)。相关分析表明,CTGF蛋白和mRNA表达与RMT和RMA呈正相关(P<0.05);TGF-β1蛋白和mRNA表达与RMT和RMA无相关性;TGF-β1 mRNA表达与CTGF mRNA表达之间无明显相关性。结论:TGF-β1和CTGF参与了大鼠高血流性肺动脉高压的病理生理过程。Objective： To evaluate the role of transforming growth factor-β1（TGF-β1） and connective tissue growth factor （CTGF） in the pathogenesis of pulmonary artery hypertension, we observed the dynamic expression of TGF-β1 and CTGF in rats with high blood flow.Methods： Fifty adult male SD rats were randomly divided into 5 groups： a sham group （group S） and groups with right pneumonectomy for 1, 2, 4 and 6 weeks （PE1, PE2, PE4 and PE6 group）, 10 rats per group. The mean pulmonary arterial pressure （mPAP）, vessel morphometry and right ventricle hypertrophy index （RVHI） were measured. TGF-β1 and CTGF protein expression in the lung tissues were determined with immunohistochemistry and Western blot. The expression of TGF-β1 mRNA and CTGF mRNA in the lung tissues was evaluated by RT-PCR. Results： Compared with group S, the mPAP and RVHI in the rats were significantly increased in group PE1, PE2, PE4, and PE6 （P〈0.05）; the indicators of vascular remodeling [（MA＋PMA）%, RMT, and RMA] were markedly elevated in group PE4 and PE6 （P〈0.05）, but not in group PE1 and PE2. Immunohistochemical staining of TGF-β1 and CTGF were more prominent in all of the right pneumonectomy groups than in the sham group. Western blot showed that the level of TGF-β1 protein was significantly increased in all of the right pneumonectomy groups （P〈0.01）, and the peak was observed in group PE2, whereas the level of CTGF protein was markedly elevated in group PE4 and PE6 （P〈0.05）, but no change was noticed in group PE1 and PE2. Compare to dramatically increased in all right pneumonectomy remained high in group PE4 and PE6. In contrast, group S, the mRNA level of TGF-β1 was groups （P〈0.01）, peaked at group PE2, and the elevation of mRNA level of CTGF was not significant in group PE1, but group PE2, PE4 and PE6 demonstrated significant mRNA level of CTGF （P〈0.01）. Correlation analysis showed that the protein and mRNA levels of CTGF were positively correlated with RMT and RMA （ r=

关 键 词：转化生长因子-Β1 结缔组织生长因子 高肺血流 肺动脉高压 

分 类 号：R363[医药卫生—病理学]