摘要
目的:观察转化生长因子β1(TGF-β1)基因动态表达变化在大鼠缺氧性肺动脉高压中的作用。方法:40只成年雄性Wistar大鼠随机分成对照组、缺氧3、7、14和21d组,每组8只,测各组大鼠平均肺动脉压(mPAP)、血管形态学指标、右室肥大指数(RVHI);原位杂交和免疫组化检测TGF-β1基因表达。结果:缺氧7d后大鼠mRNA升高(18.4±0.37)mmHg,与对照组比较差异有显著性(P<0.05),缺氧14d达高峰并维持于高水平。缺氧性肺血管重塑(HPSR)、右心室肥大于缺氧14d后出现。TGF-β1mRNA对照组中膜平滑肌细胞和外膜成纤维细胞呈弱阳性表达,缺氧3d、7d表达增高不明显,缺氧14d增高(0.385±0.028,P<0.01),并维持于高水平,TGF-β1mRNA于肺动脉中膜和外膜表达;TGF-β1蛋白在对照组呈弱阳性,缺氧3d表达增强(0.198±0.031,P<0.01),缺氧7d组达高峰(0.267±0.035,P<0.01),随着缺氧时间进一步延长,TGF-β1水平逐渐向基线水平回降,TGF-β1蛋白于肺动脉中膜和外膜表达。结论:缺氧诱导TGF-β1表达变化可能在大鼠缺氧性肺动脉高压中起到重要作用。
Objective To investigate the dynamic expression of transforming growth factor-β1(TGF-β1) in hypoxic pulmonary hypertension of rats. Methods Forty male Wistar rats were randomly exposed to hypoxia for 0, 3, 7, 14 or 21days. Mean pulmonary arterial pressure (mPAP), vessel morphometry, right ventricle hypertrophy index (RVHI) were measured. Lungs were inflation fixed for in situ hybridization and immunohistochemistry. Results The mPAP increased significantly after 7-day of hypoxia (18.41±0.37)mmHg, P< 0.05, reaching its peak after 14-day of hypoxia, then remained on the high level. Pulmonary artery remodeling index and right ventricle hypertrophy became evident after 14-day of hypoxia. Control pulmonary arteries displayed low-level expression of TGF-β1 mRNA in medial SMCs. Adventitial fibroblasts also showed a paucity of TGF-β1 mRNA, TGF-β1 mRNA expression in pulmonary arterial walls was increased significantly after 14 days of hypoxia(0.385±0.028, P< 0.01),but showed no obvious changes after 3 or 7 days of hypoxia. TGF-β1 mRNA was located predominantly in tunica adventitia and tunica media. In pulmonary tunica adventitia and tunica media, TGF-β1 staining was poorly positive in control rats, but was markedly enhanced after 3 days of hypoxia(0.198±0.031,P< 0.01), reaching its peak after 7 days of hypoxia ,then weakened after 14 and 21days of hypoxia. Conclusion The dynamic expression of TGF-β1 after hypoxia may play a important role in hypoxic pulmonary hypertension of rats.
出处
《实用医学杂志》
CAS
2005年第3期238-240,共3页
The Journal of Practical Medicine
基金
湖南省医药卫生科研基金(02-Y081)
湖南省教育厅科研基金(03C397)
湖南省医药卫生科研基金(B2004-137)
