中文摘要：

目的：研究降脂颗粒对小鼠非酒精性脂肪性肝炎（NASH）的肝纤维化的作用。方法：雄性C57BL/6小鼠24只,随机分为正常、蛋氨酸-胆碱缺乏（MCD）和降脂颗粒组。正常组小鼠予普通饲料,其余两组小鼠予MCD饲料,降脂颗粒组同时予降脂颗粒灌胃。6周后,处死各组动物并取肝组织固定或冻存。观察各组小鼠肝组织天狼猩红染色结果,用ELISA方法检测血清纤溶酶原激活物抑制因子-1（PAI-1）含量,应用荧光定量RT-PCR和/或Western blot检测肝组织PAI-1、转化生长因子-β1（TGF-β1）、α-平滑肌肌动蛋白（α-SMA）及Ⅰ型胶原α1（COL1A1）表达水平。结果：MCD组的肝组织出现广泛肝细胞脂肪变性,及窦周胶原组织增加,而降脂颗粒组肝细胞周围无明显胶原沉积。MCD组小鼠血清PAI-1含量较正常组小鼠显著升高（P〈0.001）,与MCD组比较,降脂颗粒组PAI-1含量下调（P〈0.05）。MCD组小鼠肝组织PAI-1、α-SMA、TGF-β1和COL1A1 m RNA水平均较正常组显著升高（P〈0.01,P〈0.001）,在降脂颗粒组中这些促纤维化基因的表达下调（P〈0.05）。与正常组比较,肝组织PAI-1和α-SMA蛋白表达水平在MCD组显著升高,与MCD组比较,在降脂颗粒组表达均显著下调。结论：降脂颗粒对MCD饮食诱导的小鼠NASH肝纤维化具有预防作用,其机制可能与调控NASH中肝纤维化相关因子的表达从而抑制星状细胞活化、胶原增生及促进细胞外基质降解相关。

英文摘要：

Objective： To study the effect of Jiangzhi Granule （JZ） on liver fibrosis in nonalcoholic steatotic hepatitis （NASH） mice. Methods： 24 male C57BL/6 mice were randomly divided into control group, MCD group and JZ group. Rats in the control group were fed with a standard diet, while the other groups with methionine and choline deficient （MCD） diet. And the mice of JZ group were intragastrically treated with JZ. After 6 weeks, the experimental mice were sacrificed and their livers were frozen or fixed for future use. The liver tissue slides were stained with Sirius red and observed through a microscope. The level of serum plasminogen activator inhibitor-1 （PAI-1） was detected by enzyme-linked immunosorbent assay （ELISA）. Hepatic levels of PAI-1, transforming growth factor beta 1 （TGF-β1）, alpha smooth muscle actin （α-SMA）, collagen type I, alphal （COL1A1） and β-actin were measured by quantitative RT-PCR and/or Western blot. Results： Compared with control group, the liver tissues of Sirius Red staining in MCD group showed the liver cell degeneration, and sinusoidal deposition of collagen increased, which were improved in JZ group. JZ also reversed the levels of serum PAI-1 which were significantly increased in MCD group. In addition, MCD group expressed higher level of mRNA expression of the PAI-1, α-SAM, TGF-β and COL1A1 mRNA expression, which were reduced in JZ group. MCD group expressed a higher protein level of PAI-1 and α-SMA, while decreased in JZ group. Conclusion： Jiangzhi granule could prevent early onset of liver fibrosis in mice model of NASH. The underlying mechanism might partially lie in inhibiting the activation of hepatic stellate cells and collagen production, as well as promoting the degradation of extracellular matrix, through regulating the expression of liver fibrosis-related factors in NASH pathology.