溪黄草黄酮对小鼠非酒精性脂肪肝纤维化的影响及其机制探讨

Effect of flavonoids from Rabdosia serra (Maxim) Hara on fibrosing nonalcoholic steatohepatitis in mice

目的观察不同浓度溪黄草黄酮(FRSH)对非酒精性脂肪肝纤维化小鼠的影响,并探讨初步机制。方法将小鼠随机分为5组:对照组、模型组及FRSH低、中、高剂量组(FRSH-L、FRSH-M、FRSH-H)。检测血清中丙氨酸氨基转移酶(ALT)和谷氨酸氨基转移酶(AST)水平;苏木精-伊红染色法观察肝脏组织的病理状态;Western blot检测肝组织中基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶抑制剂-1(TIMP-1)蛋白的表达;实时荧光定量聚合酶链反应(qRT-PCR)检测肝组织中转化生长因子-β(TGF-β)、过氧化物酶体增殖物活化受体-γ(PPARγ)mRNA的表达。结果与模型组比较,FRSH能够降低血清中ALT、AST的含量,并改善肝组织的脂肪变性,减轻炎症、坏死程度;肝组织中TIMP-1蛋白和TGF-β mRNA表达降低,MMP-9蛋白和PPARγ mRNA表达增加。结论 FRSH能抑制非酒精性脂肪性肝纤维化的发生、发展,可能与MMP-9、TIMP-1、TGF-β及PPARγ的表达相关。

Objective To investigate the effect of flavonoids from Rabdosia sena （Maxim） Hara （FRSH） on fibrosing nonalcoholic steatohepatitis （NASH） in mice and discuss the mechanism. Methods Mice were randomly divided into five groups： control group, model group, and treatment groups （FRSH-L, FRSH-M and FRSH-H groups）. The mice in the model group were given high-fat and methionine-choline deficient （MCD） diet. In the treatment groups MCD diet and different concentrations of FRSH were used. The serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were examined. The pathological changes of the liver were observed after HE staining. The expressions of MMP-9 and TIMP-1 in the liver were determined by Western blot. The mRNA levels of TGF-β and PPARγ were detected by qRT-PCR. Results Compared with the model group, treatment with FRSH significantly decreased the serum levels of ALT and AST and improved the liver inflammation and fibrosis. Moreover, the expressions of TIMP-1 protein and TGF- β mRNA were reduced and the expressions of MMP-9 protein and PPARγ mRNA were increased in the liver after FRSH treatment. Conclusions FRSH could retard the development of fibrosing nonalcoholic steatohepatitis through modulation of the expressions of MMP-9, TIMP-1, TGF-β and PPARγ .