西安交通大学学报（医学版）2011，Vol.32Issue(2)：215-219,5.
缺氧在大鼠肝纤维化形成中的作用机制
The role of hypoxia in formation of hepatic fibrosis in rats
邓毅恒 1窦科峰 1张色华 2张福琴 1李俊杰1
作者信息
- 1. 第四军医大学西京医院肝胆外科,陕西西安,710032
- 2. 南海区桂城医院药剂科,广东佛山,528200
- 折叠
摘要
Abstract
Objective To study the role of hypoxia in formation of hepatic fibrosis in rats. Methods Hepatic fibrosis models in rats were established by bile duct ligation (BDL), and the rats were sacrificed at postoperative day 1, 3, 7, 14, 21 and 28, respectively. Then the histopathological and ultrastructural changes were observed. Expressions of transforming growth factor-β1 (TGF-β1) and collagen Ⅰ (Coll-Ⅰ) mRNA in the whole liver were assayed by RT-PCR; the HIF-1α and α-SMA protein expressions were assayed by Western blot. Upon hypoxia,the expressions of HIF-1α, TGF-β1 and Coll-Ⅰ mRNA in rat hepatic stellate cells (HSCs) were assayed by RT-PCR,and the α-SMA protein expression was assayed by Western blot. Upon hypoxia or normoxia, the expression of Coll-Ⅰ mRNA was assayed by RT-PCR after cell culture was supplemented with neutralizing anti-TGF-β1 antibody, cobalt chloride (CoCl2) or 2-methoxyestradiol (2ME2). Results ① Electron microscopy showed that hypoxia and energy metabolism dysfunction appeared in the rat livers in the early stage after surgery. ② HIF-1α protein expression was increased 3 days after surgery; TGF-β1, Coll-Ⅰ mRNA and α-SMA protein expressions were increased 7 days after surgery. ③ Hypoxia induced the elevation of HIF-1α, TGF-β1, Coll-Ⅰ mRNA and α-SMA protein expressions in HSCs. ④ In normoxia, CoCl2could induce the expression of Coll-Ⅰ mRNA; in contrast, neutralizing anti-TGF-β1 antibody and 2ME2 inhibited the expression of Coll-Ⅰ mRNA upon hypoxia. Conclusion Hypoxia activates HSC and increases the production of Coll-Ⅰ via TGF-β1-dependent and HIF-1α-dependent signaling pathway. Therefore, hypoxia may play an important role in the development of hepatic fibrosis.关键词
肝纤维化/缺氧/缺氧诱导因子-1α/转化生长因子-β1/肝星状细胞分类
医药卫生引用本文复制引用
邓毅恒,窦科峰,张色华,张福琴,李俊杰..缺氧在大鼠肝纤维化形成中的作用机制[J].西安交通大学学报（医学版）,2011,32(2):215-219,5.
