肝脏结合盒转运子G5和G8的表达与肝移植后胆汁中胆固醇分泌无关  

Hepatic expression of ABC transporters G5 and G8 does not correlate with biliary choles-terol secretion in liver transplant patients

作　　者：Geuken E. Visser D.S. Leuvenink H.G.D. R.J. Porte 孟欣颖 

机构地区：[1]Department of Surgery, Section Hepatobiliary Surgery and Liver Transplantation,University Medical Center, Groningen, P.O. Box 30.001, 9700 RB Groningen, Netherlands Dr.

出　　处：《世界核心医学期刊文摘（胃肠病学分册）》2006年第5期44-45,共2页Core Journals in Gastroenterology

摘　　要：The adenosine triphosphate (ATP) binding cassette (ABC) transporters ABCG5 and ABCG8 have been shown to mediate hepatic and intestinal excretion of cholesterol. In various (genetically modified) murine models, a strong relationship was found between hepatic expression of ABCG5/ABCG8 and biliary cholesterol content. Our study aimed to relate levels of hepatic expression of ABCG5 and ABCG8 to biliary excretion of cholesterol in man. From 24 patients who had received a liver transplant, bile samples were collected daily after transplantation over a 2-week period to determine biliary composition. Expression of ABCG5, ABCG8, MDR3, and BSEP was assessed by real-time polymerase chain reaction (PCR) in liver biopsy specimens collected before and after transplantation. Levels of hepatic ABCG5, ABCG8, and MDR3 messenger RNA (mRNA) were strongly correlated. After transplantation, the biliary secretion rate of cholesterol continuously increased, coinciding with gradual increases in bile salt and phospholipid secretion. In contrast, hepatic levels of ABCG5 and ABCG8 mRNA remained unchanged. Surprisingly, no correlation was found between the hepatic expression of ABCG5 and ABCG8 and rates of biliary cholesterol secretion, normalized for biliary phospholipid secretion. As expected, the concentration of biliary phospholipids correlated well with MDR3 expression. In conclusion, the strong relationship between ABCG5 and ABCG8 gene expression is consistent with the coordinate regulation of both genes, and in line with heterodimerization of both proteins into a functional transporter. Hepatic ABCG5/ABCG8 expression, at least during the early phase after transplantation, is not directly related to biliary cholesterol secretion in humans. This finding suggests the existence of alternative pathways for the hepatobiliary transport of cholesterol that are not controlled by ABCG5/ABCG8.The adenosine triphosphate （ATP） binding cassette （ABC） transporters ABCG5 and ABCG8 have been shown to mediate hepatic and intestinal excretion of cholesterol. In various （genetically modified） murine models, a strong relationship was found between hepatic expression of ABCGS/ABCG8 and biliary cholesterol content. Our study aimed to relate levels of hepatic expression of ABCG5 and ABCG8 to biliary excretion of cholesterol in man. From 24 patients who had received a liver transplant, bile samples were collected daily after transplantation over a 2- week period to determine biliary composition. Expression of ABCGS, ABCG8, MDR3, and BSEP was assessed by real-time polymerase chain reaction （PCR） in liver biopsy specimens collected before and after transplantation. Levels of hepatic ABCGS, ABCG8, and MDR3 messenger RNA （mRNA） were strongly correlated. After transplantation, the biliary secretion rate of cholesterol continuously increased, coinciding with gradual increases in bile salt and phospholipid secretion. In contrast, hepatic levels of ABCG5 and ABCG8 mRNA remained unchanged. Surprisingly, no correlation was found between the hepatic expression of ABCG5 and ABCG8 and rates of biliary cholesterol secretion, normalized for biliary phospholipid secretion. As expected, the concentration of biliary phospholipids correlated well with MDR3 expression. In conclusion, the strong relationship between ABCG5 and ABCG8 gene expression is consistent with the coordinate regulation of both genes, and in line with heterodimeriza- tion of both proteins into a functional transporter.

关 键 词：胆汁标本 人肝脏 胆固醇 分泌率 移植后 转运子 三磷酸腺苷(ATP) mRNA水平 ABCG8 ABCG5 

分 类 号：R446.5[医药卫生—诊断学] R392-33[医药卫生—临床医学]