缺氧诱导因子-1α及其下游分子在大鼠肝纤维化组织中的表达

Expression of HIF-1α and its downstream molecules in rat liver fibrosis tissue

目的观察缺氧诱导因子-1α(HIF-1α)及其下游分子在大鼠肝纤维化组织中的表达情况,分析HIF-1α及其下游分子与肝纤维化程度的关系。方法用CCl4诱发大鼠肝纤维化模型,建模结束后(实验8周末)根据纤维化程度将模型组分为S2、S3、S4亚组,然后分别应用免疫组织化学和逆转录酶PCR方法检测HIF-1α、基质金属蛋白酶-2(MMP-2)、血管内皮生长因子(VEGF)蛋白和HIF-1α、MMP-2 mRNA在大鼠肝纤维化组织中的表达变化。结果与对照组(S0组)比较,模型组(S2、S3、S4亚组)HIF-1α、MMP-2、VEGF蛋白和HIF-1α、MMP-2 mRNA表达均明显增强(P<0.01);HIF-1α、MMP-2、VEGF的表达与肝纤维化程度呈正相关(r值分别为0.923、0.848、0.878,均P<0.001);MMP-2、VEGF的表达与HIF-1α也呈正相关(r值分别为0.862、0.993、0.892,均P<0.001)。结论HIF-1α可能通过调节MMP-2及VEGF的表达促进了肝纤维化的发展。

Objective To observe the changes of hypoxia inducible factor-1 a （HIF-1 a ）and its downstream molecules in rat liver fibrosis tissue, and to clarify the relationship between liver fibrosis and them. Methods The hepatic fibrosis model of the rats was induced by CCl4. and the model group was divided into three subgroups（S2,S3, S4 ）,according to the degree of the liver fibrosis after the experiment over（at the 8th weekend）. Then the expression of HIF- 1 α, matrix metalloproteinase- 2 （ MMP-2 ）, vascular endothelial growth factor （VEGF） protein and HIF-1 α, MMP-2 mRNA were detected by immunohistochemistry and RT-PCR in rat fibrotic liver tissues. Results The expression of HIF-1 α, MMP-2, VEGF protein and HIF-1 α, MMP-2 mRNA significantly increased in the model group （S2, S3, S4 subgroups） （ P 〈 0.01 ）, compared with normal group （So group）. There was a remarkable positive correlation between the expression of HIF-la, MMP-2, VEGF and the degree of liver fibrosis （ r = 0. 923,0. 848, 0. 878, respectively, P 〈 0.01 ）, and there was a remarkable positive correlation between the expression of MMP-2, VEGF and of HIF-1 α （ r= 0. 862, 0. 995, 0. 892, respectively, P 〈 0.01 ）. Conclusion It is probably that HIF-1 α promotes the development of liver fibrosis by inducing the expression of MMP-2, VEGF.