绿原酸对胆管结扎大鼠肝毒性和胆汁淤积的胆汁酸和胆红素转运及代谢的调节作用：涉及 SIRT1 介导的 FXR 和 PGC-1α 去乙酰化。
Modulation of transport and metabolism of bile acids and bilirubin by chlorogenic acid against hepatotoxicity and cholestasis in bile duct ligation rats: involvement of SIRT1-mediated deacetylation of FXR and PGC-1α.
机构信息
Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
出版信息
J Hepatobiliary Pancreat Sci. 2018 Mar;25(3):195-205. doi: 10.1002/jhbp.537.
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.
背景
本研究旨在探讨绿原酸（CA）对胆管结扎（BDL）大鼠模型胆汁淤积性肝损伤的作用及潜在机制。
方法
大鼠连续 3 天口服给予载体或 CA（20、50 或 100mg/kg/天）。第 4 天，大鼠行假手术或 BDL 手术，术后连续 3 天或 7 天给予载体或 CA。通过 qRT-PCR 和 Western blot 评估 mRNA 和蛋白表达水平。
结果
BDL 后，血浆丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆红素（TBIL）和总胆汁酸（TBA）水平升高，肝组织形态学出现典型病变。肝摄取转运体（Ntcp、Oatp1a4 和 Oatp1b2）表达下调，而胆汁外排转运体（Bsep 和 Mrp2/3/4）表达上调。BDL 抑制 Cyp7a1、Cyp8b1 和 Cyp27a1 的表达并诱导 Ugt1a1。CA 治疗降低了 ALT、AST、TBIL 和 TBA（P<0.05）并减轻了肝组织病理变化。CA 进一步扩大了转运体和酶的表达变化程度（P<0.05）。CA 处理后 BDL 大鼠 SIRT1 蛋白表达增加。
结论
CA 通过减少胆红素和胆汁酸的摄取和合成，加速胆红素和胆汁酸的代谢和外排，减轻肝毒性和胆汁淤积。
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