Transforming growth factor-β_1 expresses in hypoxic pulmonary hypertension in rats

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.