基于血清代谢组学研究佛手柑内酯治疗肝纤维化的作用机制OA北大核心CSTPCD

OBJECTIVE To study the effects of bergapten in the treatment of liver fibrosis and its mechanism based on serum metabolomics.METHODS Forty mice were divided into normal control group(0.5%carboxymethyl cellulose sodium solution),model group(0.5%carboxymethyl cellulose sodium solution),and BP low-dose and high-dose groups(50,100 mg/kg),with 10 mice in each group.Except for the normal control group,the other three groups were all treated with carbon tetrachloride to induce liver fibrosis model;they were given relevant medicine/solution intragastrically,once a day,for consecutive 8 weeks.After the last medication,the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum were detected,and liver pathological changes were observed;the expressions of α-smooth muscle actin(α-SMA)and Collagen Ⅰ were detected in liver tissue;the serum of the mice was collected for metabolomics analysis.RESULTS Compared with the model group,serum levels of ALT and AST and protein expressions of α-SMA and Collagen Ⅰ in liver tissue were decreased significantly in BP high-dose and low-dose groups(P＜0.05),while liver fibrosis was improved significantly.Meanwhile,metabolomics analyses showed that there were a total of 175 serum differential metabolites in the BP high-dose group and model group,of which 18 substances were upregulated and 157 substances were downregulated;the main metabolic pathways involved in bergapten intervention were pyrimidine metabolism,butanoate metabolism,fatty acid synthesis,tyrosine metabolism,β-alanine metabolism,nicotinic acid and nicotinamide metabolism,glutathione metabolism,etc.CONCLUSIONS BP is effective in the treatment of liver fibrosis by regulating pyrimidine metabolism,butanoate metabolism,glutathione metabolism and so on in rats with liver fibrosis.