Protective Effects of Matrine on α-Naphthl Isocyanate-Induced Cholestatic Liver Injury in Rats / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the preventive protective effect of matrine(MT) on α-naphthl isocyanate(ANIT)-induced cholestasis in rat, and to explore its possible mechanism. METHODS: Thirty SD rats were randomly divided into five groups with six rats in each group normal control group, model group, low dose matrine(5 mgkg-1), high dose matrine group(10 mgkg-1) and positive control group(ursodeoxycholic acid 100 mgkg-1), which were administered continuously for 7 d. All groups except the normal control group were given 60 mgkg-1 ANIT at the fifth day. After the last administration, all rats were fasted 24 h and arterial blood were collected to detect the indexes of total bilirubin(TBIL), aspartate aminotransferase(AST), alanine aminotransferase(ALT) and alkaline phosphatase(ALP). The livers were picked for HE staining, immunohistochemistry(IHC) analysis and Western blot(WB), to indentify the protein expressions of CYP3A4 and PXR. RESULTS: Compared to model group, low-dose and high-dose matrine decreased TBIL, AST, ALT and ALP significantly; IHC analysis showed that the expression of CYP3A4 in high-dose group was significantly higher than that in model group(P<0.05). The results of WB showed that the expressions of CYP3A4 and PXR in two matrine groups were significantly higher than that in model group(P<0.05), however, only CYP3A4 expression in UDCA group was significantly higher than that in model group(P<0.05). CONCLUSION: Matrine could improve cholestatic liver injury in rats and its mechanism might be related to the upregulation of CYP3A4 expression controled by inducing PXR expression.