The Protective Effect And Mechanism Of Ligustrazine On Nrf2/ARE Pathway In Liver Tissue Of Hepatic Fibrosis Rats Induced By CCl₄

[Objective] To explore the effect of ligustrazine on Nrf2/ARE pathway in liver tissue of hepatic fibrosis rats induced by CCl4for studying the mechanism of its effect on hepatic fibrosis. In order to provide sufficient experimental basis for the clinical treatment of liver fibrosis.[Methods] Hepatic fibrosis in rats was induced by carbon tetrachloride. Twenty-four male SD rats (200±20g) were adaptively fed for a week, then randomly divided into normal control group, hepatic fibrosis group and treatment group. They were in turn named A、B、C group. For the first time, B、C groups were given carbon tetrachloride of5ml/kg weight subcutaneously. Then given mixture of CC14/vegetable oil of3ml/kg weight. Treatment group rats were given ligustrazine of60mg/kg weight intraperitoneally everyday while inducing hepatic fibrosis by carbon tetrachloride. A group was given an equal volume of vegetable oil and saline. After six weeks, under pyrogen-free condition, 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. malondialdehyde(MDA) in liver tissues were measured with TBA method, glutathione S-transferase(GST) by colorimetric enzymatic assay. The distribution and expression of Nrf2were detected by immunohistochemistry. Nrf2protein expression in liver tissues was detected by Western-blotting method.[Results] Fibrosis model group compared with normal control group:①The content of plasma endotoxin was increased;②The contents of hydroxyproline, MDA and GST in liver tissues were significantly increased;③Pathological damage of liver tissues was worse. The content of collagen was significantly increased;④The results of immunohistochemistry and Western-blotting show that:just a small amount of Nrf2was expressed in normal liver tissues, but significantly increased in fibrosis model group. Ligustrazine group compared with the hepatic fibrosis model group:①The content of plasma endotoxin was reduced;②The contents of MDA and hydroxyproline in liver tissues were significantly reduced;③The content of GST was significantly increased;④Pathological damage of liver tissues was less. The content of collagen was significantly decreased;⑤The expression of Nrf2in liver tissues was significantly increased.[Conclusions] The protective effect of ligustralzine on liver fibrosis is possible related to reducing endotoximia, promoting the nuclear translocation of Nrf2and activating Nrf2/ARE pathway in liver, thus increasing the content of antioxidant enzymes such as GST.