雌二醇对大鼠肝星状细胞MMP-2、TIMP-1表达的影响

The effect of estradiol on the expression of MMP-2 and TIMP-1 in rat hepatic stellate cells

目的探讨雌二醇对肝星状细胞（HSC）的影响及其可能的作用途径。方法培养大鼠HSC，初次传代后，HSC随机分为4组，分别加入不同浓度的雌二醇，噻唑蓝（MTT）法检测雌二醇对HSC增殖的影响；逆转录-聚合酶链式反应（RT—PCR）分析其对HSC的基质金属蛋白酶因子（MMP-2）、组织金属蛋白酶抑制剂（TIMP-1）的mRNA表达的影响；免疫细胞化学分析其对HSC的α—SMA蛋白的表达的影响。结果MTT法发现雌二醇抑制HSC的增殖，并且随浓度增加抑制作用增强，与阳性对照组比较雌二醇干预组HSCMMP-2mRNA表达增加（P〈0．01），TIMP—1mRNA的表达下降（P〈0．01），α-SMA蛋白表达明显下降（P〈0．05）。结论雌二醇具有抑制肝纤维化作用是因为：①可以抑制HSC的增殖、活化；②促进MMP-2mRNA的表达，抑制了TIMP-1mRNA的表达。

Objective To analyze the effect and the pathway of estradiol on hepatic stellate cells （HSC）. Methods Cultured HSC were randomly divided into 4 groups and different concentrations of estradiol were added, then the effect of estradiol on the proliferation and the expression of MMP-1 and TIMP-1 mRNA, and α - SMA protein were detected by MTT assay, RT-PCR and Immunocytochemistry, respectively. Results The results showed that estradiol could inhibit HSCs proliferation in the dose-dependent manner. We found that estradiol up regulated the expression of MMP-2 （P〈 0.01） and down-regulated the expression of TIMP-1 in mRNA level （P 〈 0.01）. The expression of α -SMA protein significantly decreased as compared with the negative control （P〈 0. 05）.Conclusion Estradiol has anti-fibrosis function. This maybe related to increase the expression of MMP-2 and decrease the expression of TIMP-1.