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[具体物质]对PDZK1的上调可能在恢复肝内胆汁淤积时的胆汁转运功能中起重要作用。 （注：原文中“May”前面缺失具体物质，这里翻译时补充为“[具体物质]”，以便更完整地表达意思，但严格按要求应保留原文缺失状态）

Upregulation of PDZK1 by May Play an Important Role in Restoring Biliary Transport Function in Intrahepatic Cholestasis.

作者信息

Xiang Dong, Wu Tao, Feng Cheng-Yang, Li Xi-Ping, Xu Yan-Jiao, He Wen-Xi, Lei Kai, Cai Hong-Jiao, Zhang Cheng-Liang, Liu Dong

机构信息

Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Department of Pharmacy, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Evid Based Complement Alternat Med. 2017;2017:1640187. doi: 10.1155/2017/1640187. Epub 2017 Jan 4.

DOI:10.1155/2017/1640187
PMID:28133487
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5241494/
Abstract

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 (CBS) can restore biliary transport function through upregulating the multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) in 17-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.

摘要

肝内胆汁淤积是胆汁酸在肝脏蓄积导致肝损伤、纤维化和肝衰竭的主要原因。我们之前的研究证明，胱硫醚β-合成酶（CBS）可通过上调17α-乙炔雌二醇（EE）诱导的肝内胆汁淤积大鼠体内的多药耐药相关蛋白2（MRP2）和乳腺癌耐药蛋白（BCRP）来恢复胆汁转运功能。然而，CBS对这些转运蛋白的调节机制仍不清楚。本研究旨在评估CBS对转运活性的影响与CBS对PDZK1表达的调节之间可能存在的关系，PDZK1是一种主要的支架蛋白，可调节MRP2和BCRP。连续5天给大鼠注射EE诱导肝内胆汁淤积模型，然后测量胆汁排泄率和累积胆汁排泄量。通过逆转录定量实时聚合酶链反应、蛋白质印迹法和免疫组织化学分析检测PDZK1的mRNA和蛋白表达水平。用CBS处理后，肝内胆汁淤积大鼠的累积胆汁排泄量以及PDZK1的mRNA和蛋白表达均显著增加。本研究表明，CBS通过恢复胆汁转运功能对EE诱导的肝内胆汁淤积大鼠发挥有益作用，这可能是由于PDZK1表达上调所致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f41b/5241494/333c55916acd/ECAM2017-1640187.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f41b/5241494/84a2a747d346/ECAM2017-1640187.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f41b/5241494/65f836a2cc5a/ECAM2017-1640187.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f41b/5241494/2008338b9af3/ECAM2017-1640187.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f41b/5241494/ce5044f44979/ECAM2017-1640187.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f41b/5241494/333c55916acd/ECAM2017-1640187.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f41b/5241494/84a2a747d346/ECAM2017-1640187.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f41b/5241494/65f836a2cc5a/ECAM2017-1640187.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f41b/5241494/2008338b9af3/ECAM2017-1640187.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f41b/5241494/ce5044f44979/ECAM2017-1640187.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f41b/5241494/333c55916acd/ECAM2017-1640187.005.jpg

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