目的：观察川芎嗪对四氯化碳诱导的肝纤维化大鼠肝组织Nrf2/ARE信号通路的影响,探讨川芎嗪治疗肝纤维化的作用机制。方法四氯化碳皮下注射制备大鼠肝纤维化模型,设立正常对照组、肝纤维化模型组和川芎嗪治疗组,川芎嗪治疗组在造模过程中每天给予盐酸川芎嗪注射液腹腔注射,6周后,乙醚麻醉,腹主动脉采血,产色基质偶氮法鲎试剂定量测定血浆内毒素；肝组织常规HE染色观察肝脏病变,天狼猩红胶原染色、肝组织羟脯氨酸含量测定评测肝纤维化程度；West-blotting法检测肝组织内Nrf2蛋白的表达, TBA法检测肝组织丙二醛(MDA)水平,酶显色定量分析法检测肝组织谷胱甘肽-S-转移酶(GST)含量。结果川芎嗪治疗组与肝纤维化模型组相比,肝损伤较轻,肝纤维化程度明显降低,血浆内毒素含量降低, Nrf2蛋白表达量增多,肝组织中MDA含量降低, GST的含量升高。结论川芎嗪的抗肝纤维化作用可能与其降低内毒素血症,激活肝内Nrf2/ARE抗氧化通路进而使得抗氧化酶GST等含量增加有关。%Objective To explore the effect of ligustrazine on Nrf2/ARE pathway in liver tissue of hepatic fibrosis rats induced by CCl4 for studying the mechanism of its effect on hepatic fibrosis. Methods Hepatic fibrosis in rats was induced by carbon tetrachloride, rats were randomly divided into normal control group, hepatic fibrosis group and treatment group. treatment group rats were given ligustrazine intraperitoneally everyday while inducing hepatic fibrosis by carbon tetrachloride. After 6 weeks, rats were killed for collecting blood and liver tissues. Endotoxin in blood plasma was measured with a limulus amebocyte lysate test kit. The pathological changes of liver were observed by hematoxylin-eosin staining, the degree of liver fibrosis was assessed by stained of Sirius red for collgen and the contents of hydroxyproline in liver tissues. Nrf2 protein expression in liver tissues was detected by West-blotting method. The contents of malondialdehyde(MDA) in liver tissues were determined by TBA method, glutathione S-transferase(GST) by colorimetric enzymatic assay. Results Fibrotic changes in liver of treatment group were ameliorated significantly compared with the hepatic fibrosis model group, and the content of plasma endotoxin were reduced, liver expression of Nrf2 was increased as well as GST, MDA was reduced accordingly. Conclusion The protective effect of ligustrazine on liver fibrosis is possibly related to reducing endotoximia and activating Nrf2/ARE pathway in liver, thus increasing the content of antioxidant enzymes such as GST.
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