同型半胱氨酸诱导肝星状细胞激活和增殖在肝纤维化发生中的作用

Activation and Proliferation of Hepatic Stellate Cells Induced by Homocysteine in Hepatic Fibrosis

目的探讨同型半胱氨酸诱导肝纤维化的机制.方法采用高甲硫氨酸喂养小鼠,制成高同型半胱氨酸血症模型;采用HE染色检测肝组织纤维化;肝星状细胞周期蛋白D1基因表达升高测定采用RT-PCR.结果高甲硫氨酸饮食造成小鼠同型半胱氨酸血症,导致诱导肝纤维化;同型半胱氨酸处理肝星状细胞,导致周期蛋白D1表达升高;同型半胱氨酸的作用可被抗氧化剂维生素E和TEMPO所抑制.结论同型半胱氨酸诱导肝纤维化作用与促进肝星状细胞激活和增殖有关,活性氧自由基参与了这一过程.

Objective To study the mechanism of hepatic fibrosis induced by homocysteine. Methods Mice were fed high-methionine diet to induce hyperhomocysteinemia; Fibrosis in liver tissues was detected by using HE staining; The mRNA levels of cyclin D1 were detected by RT-PCR. Results Hyperhomoeysteinemia in mice induced by high-methionine diet enhanced hepatic fibrosis. Treatment of homocysteine with hepatic stellate cells （HSCs） resulted in an increase in the expression of cyclin D1. The up-regulation of cyclin l expression by homocysteine was inhibited by antioxidants vitamin E and TEMPO. Conclusions Hepatic fibrosis induced by homocysteine is associated with the activation and proliferation of HSC. Reactive oxygen species are involved in this process.