悦肝胶囊对肝纤维化大鼠防治作用的实验研究

目的:观察悦肝胶囊对二甲基亚硝胺(DMN)模型大鼠肝纤维化形成的影响,探讨悦肝胶囊抗肝纤维化的作用机制。方法:模型制备采用DMN4周12天腹腔注射,实验组分别用大、中、小剂量悦肝胶囊干预,干扰素对照。生化测定肝组织羟脯氨酸含量(HYP);免疫组织化学方法观察α-平滑肌肌动蛋白(α-SMA),基质金属蛋白酶-1(MMP-1)及其抑制剂(TIMP-1)的表达情况;通过天狼猩红染色和HE染色观察肝组织胶原沉积情况及病理变化。结果:与模型对照组相比,悦肝胶囊可有效改善肝组织胶原沉积,降低肝组织HYP含量,抑制肝组织α-SMA和TIMP-1表达,对MMP-1表达影响微弱,无差异。结论:提示悦肝胶囊具有保肝和抗肝纤维化作用,作用机制可能与其抑制肝星状细胞(HSC)活化,减少胶原合成,同时促进胶原分解有关。

The Protective Effects of Yuegan Capsule on Dimethylnitrosamine-induced Hepatic Fibrosis in Rats

Objective:To investigate the effects and me-chanisms of Yuegan capsule on liver fibrosis induced by dimethylnitrosamine (DMN) in rats. Methods: the animal models were made with 0.5% DMN ip. 3 days every week for 4 weeks. During the time, Yuegan capsule was administrated at the high dose, middle dose and small dose once a day compared with recombinant human interferon α-2a for injection. We detected and measured the content of in liver homogenate, and observed alpha-smooth muscle actin (α-SMA), matrix metalloproteinase-1 (MMP-1) and the tissue inhibitor of metalloprotei-nase-1(TIMP-1) by immunohistochemical method. The liver pathological changes and the deposition of collagen were observed with HE and Sirius red staining. Results: compared with the model group, Yuegan capsule could decrease the deposition of collagen and the content of hydroxyproline efficiently in liver, and inhibit alphasmooth muscle actin (α-SMA) and the tissue inhibitor of metalloproteinase-1 (TIMP-1). MMP-1 in all groups were slight and have no distinct dis-crepancy. Conclusions: Yuegan capsule is effective in protecting against DMN-induced liver fibrosis in rats. The mechanisms of the protection may due to in-hibit the activity of hepatic stellate cell (HSC), then reduce the synthesis of the collagen and promote its degradation.