Upregulation of PDZK1 by Calculus Bovis Sativus May Play an Important Role in Restoring Biliary Transport Function in Intrahepatic Cholestasis.
Upregulation of PDZK1 by Calculus Bovis Sativus May Play an Important Role in Restoring Biliary Transport Function in Intrahepatic Cholestasis.
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牛黄上调 PDZK1 可能在肝内胆汁淤积恢复胆汁运输功能中发挥重要作用
DOI：
10.1155/2017/1640187
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Liu D
中科院分区：
文献类型：
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作者：
Xiang D;Wu T;Feng CY;Li XP;Xu YJ;He WX;Lei K;Cai HJ;Zhang CL;Liu D
肝内胆汁淤积是肝脏胆汁酸积聚的主要原因，导致肝损伤、肝纤维化和肝功能衰竭。我们以往的研究证明，牛黄通过上调17-α-乙炔雌二醇(EE-)诱导的肝内胆汁淤积大鼠的多药耐药相关蛋白2和乳腺癌耐药蛋白来恢复胆汁转运功能。然而，CBS对这些转运蛋白的调控机制尚不清楚。本研究旨在探讨CBS对转运活动的影响与CBS对PDZK1表达的调节之间的可能关系。PDZK1是调节MRP2和BCRP的主要支架蛋白。连续5d注射EE建立大鼠肝内胆汁淤积模型，测定胆汁排泄率和累积胆汁排泄量。采用逆转录-实时定量聚合酶链式反应、Western印迹和免疫组织化学方法检测PDZK1的mRNA和蛋白表达水平。给予CBS治疗后，肝内胆汁淤积症大鼠胆汁累积排泄量及PDZK1的mRNA和蛋白表达均显著增加。提示CBS对EE诱导的肝内胆汁淤积大鼠有一定的保护作用，其机制可能与上调PDZK1的表达有关。
Intrahepatic cholestasis is a main cause of hepatic accumulation of bile acids leading to liver injury, fibrosis, and liver failure. Our previous studies proved that Calculus Bovis Sativus (CBS) can restore biliary transport function through upregulating the multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) in 17α-ethynylestradiol- (EE-) induced intrahepatic cholestasis rats. The regulation mechanism of CBS on these transporters, however, remains unclear. This study was designed to evaluate the possible relationship between the effect of CBS on transport activities and the regulation of CBS on the expression of PDZK1, a mainly scaffold protein which can regulate MRP2 and BCRP. Intrahepatic cholestasis model was induced in rats with injection of EE for five consecutive days and then the biliary excretion rates and cumulative biliary excretions were measured. The mRNA and protein expression levels of PDZK1 were detected by reverse transcription-quantitative real-time polymerase chain reaction, western blot, and immunohistochemical analysis. When treated with CBS, cumulative biliary excretions and mRNA and protein expressions of PDZK1 were significantly increased in intrahepatic cholestasis rats. This study demonstrated that CBS exerted a beneficial effect on EE-induced intrahepatic cholestasis rats by restoring biliary transport function, which may result from the upregulation of PDZK1 expression.