胆汁淤积
胆红素
内科学
肝损伤
胆汁酸
CYP8B1
化学
内分泌学
胆管
多药耐药蛋白2
新陈代谢
胆固醇7α羟化酶
药理学
生物化学
运输机
医学
ATP结合盒运输机
基因
作者
Lili Zhu,Lei Wang,Fei Cao,Peng Liu,Hanying Bao,Yumei Yan,Xin Dong,Dong Wang,Zhongyu Wang,Peng Gong
摘要
Abstract Background The purpose of the present study was to investigate the effect and potential mechanism of chlorogenic acid (CA) on liver injury induced by cholestasis in a rat model of bile duct ligation (BDL). Methods Rats received vehicle or CA (20, 50, or 100 mg/kg per day) orally for 3 days. On the 4th day, the rats underwent sham or BDL surgery, and were orally administrated vehicle or CA for 3 or 7 days. mRNA and protein expression levels were evaluated by qRT‐PCR and western blot. Results After BDL, plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and total bile acids (TBA) were increased and typical pathological changes were observed in liver morphology. Hepatic uptake transporters (Ntcp, Oatp 1a4, and Oatp 1b2) were downregulated, while efflux transporters (Bsep and Mrp 2/3/4) were upregulated. BDL inhibited the expressions of Cyp7a1, Cyp8b1, and Cyp27a1 and induced Ugt1a1. CA treatment decreased ALT, AST, TBIL, and TBA ( P < 0.05) and alleviated the liver pathological changes. The degree of expression changes in the transporters and enzymes was extended by CA ( P < 0.05). SIRT1 protein was induced after CA treatment in BDL rats. Conclusions Chlorogenic acid attenuated hepatotoxicity and cholestasis by decreasing the uptake and synthesis of bilirubin and bile acids and accelerating the metabolism and efflux of bilirubin and bile acids.
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