缺氧诱导因子-1α、血管内皮生长因子在兔早期肝硬化形成过程中的表达

Expression of HIF-1α and VEGF in early stage of cirrhosis of rabbits

目的观察兔早期肝硬化形成过程中缺氧诱导因子（HIF）-lα、血管内皮生长因子（VEGF）在肝组织的表达。方法实验设四氯化碳诱导和正常对照组各15只新西兰大白兔，分别每2周处死实验组3只，正常对照组3只，同时进行常规病理学检测及免疫组织化学检测。结果HIF-1α免疫组织化学染色阳性细胞主要位于肝细胞的细胞质中，部分细胞核中也有表达。VEGF免疫组织化学染色阳性细胞位于肝细胞的细胞质、细胞核和血管内皮细胞中。HIF—lα、VEGF阳性表达均呈棕黄色颗粒。HIF-lα、VEGF在早期肝硬化期（12周末）阳性表达数均为10例；在肝纤维化期（8周末）阳性表达数均为9例；在肝炎期（4周末）阳性表达数均为4例。HIF-1α mRNA、VEGF mRNA在3个时期表达水平差异有统计学意义（P〈0．05），并随时间延长其阳性表达率增加。结论通过对兔早期肝硬化形成过程中HIF-1α、VEGF在肝组织的表达的观察，为临床基因靶点治疗肝脏疾病提供实验基础。

Objective To investigate the expression of hypoxia-inducible factor-lα （HIF-1α） and vascular endothelial growth factor （VEGF） in liver tissue at early stage of cirrhosis of rabbits. Meth. ods Fifteen New Zealand Rabbits of control group and 15 of test group were used in this study. The rabbits in the test group were induced with CC14,and 3 in each group were studied with routine pathological test and immunohistochemistry （IHC） with 2 weeks intervals. Results In HIF-lα test, IHC staining-posi- tive ceils were observed mainly in cytoplasm of liver ceils with the finding also in part of cellular nuclei, and in VEGF test,IHC staining-positive ceils were observed in liver ceil cytoplasm, nucleus and vascular endothelium. HIF-lα- and VEGF-positive cells showed brown-yellow granules. HIF-lα- and VEGF -posi- tive animals were both 10 in early stage of cirrhosis （the ends of lOth and 12th weeks） ,both 9 in liver fibrosis stage （the ends of 6th and 8th weeks）, both 4 in stage of hepatitis （ the ends of 2nd and 4th weeks）. The expression levels of HIF-lα mRNA and VEGF mRNA showed statistically signuificant difference （P〈0.05） ,and positive rate of them was gradually enhanced. Conclusion This study on the ex- pression of HIF-lα and VEGF in liver tissue in the process of early-stage cirrhosis provides theoretical basis for clinical gene-targeted treatment of liver diastases.