胆固醇结石病人肝脏脂质代谢异常的分子生物学研究  

Identification of the molecular defects in the liver underlying gallstone disease in non-obese Chinese patients

作　　者：蒋兆彦[1] 姜翀弋[1] 胡海 所广军 Paolo Parini Gsta Eggertsen Matthew A Davis Lawrence L Rudel Curt Einarsson 韩天权[1] 张圣道[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院外科上海消化外科研究所 [2]上海东方医院外科 [3]Division of Hepatology and Gastroenterology,Department of Medicine,Karolinska University Hospital Huddinge,141 86 Stockholm,Sweden [4]Department of Pathology,Section on Lipid Sciences,Wake Forest University School of Medicine,Winston-Salem,North Carolina,27157

出　　处：《外科理论与实践》2007年第5期414-421,共8页Journal of Surgery Concepts & Practice

基　　金：中国国家自然科学基金(No30271272;No30672042);瑞典Swedish Research Council;Swedish Medical Association;Swedish Heart-Lung and the Throne Holst Foundations;Ruth and Richard Julin Foundation;美国NIH(HL-49373)。

摘　　要：目的:研究导致胆石病人胆汁胆固醇过饱和的肝脏胆固醇和胆汁酸代谢途径中的分子生物学改变。方法:收集22例胆石病人和13例无胆石病的对照病人肝脏活检组织、胆囊胆汁和血浆。采用实时定量PCR检测肝脏基因表达,采用Western印迹法测定蛋白含量。结果:胆石病人较对照组ABCG5/ABCG8和LXRα基因的mRNA表达水平分别增加51%、59%和102%。肝脏SRBI的mRNA和蛋白含量均增加。结论:胆石病人ABCG5/ABCG8基因表达上调,可能与LXRα表达增加促进相关,这些异常是导致胆汁胆固醇过饱和的原因。此外,胆汁中过多的胆固醇可能来源于经肝脏高密度脂蛋白受体SRBI的摄取,而不是由于肝脏合成和酯化的异常。Objective To investigate the hepatic expression of genes involving in the metabolism of cholesterol and bile acids which lead to cholesterol supersaturation of the bile in Chinese patients with gallstones. Methods Twenty-two non-obese normolipidemic patients （female/male 11/11） with gallstones （GS） from Shanghai, China, were investigated together with 13 gallstone-free controls （matched by age and body mass index; female/male 10/3）. Liver biopsies, gallbladder bile and serum samples were collected. Gene expression was performed by real-time PCR, bile acids and cholesterol metabolites by mass spectrometry, and proteins by Western blotting. Results The bile from the gallstone patients had higher cholesterol saturation than the controls. The mRNA levels of ABCG5/ABCG8, and LXRα in the GS patients were increased by 51%, 59% and 102% respectively, and the mRNA levels correlated well with both the molar % of biliary cholesterol and cholesterol saturation index. The mRNA and protein levels of the hepatic scavenger receptor B type I （SRBI） both were increased, and a significant correlation was found between the protein levels and the cholesterol saturation index. No differences were noted between the two groups concerning the hepatic synthesis of cholesterol and bile acids, and esterification of cholesterol. Conclusions The upregulation of ABCG5/ABCG8 in the GS patients, possibly mediated by increased LXRα expression, may account for the cholesterol supersaturation of the bile. The increased amounts of biliary cholesterol may orginate from plasma high-density lipoprotein（HDL） cholesterol by enhanced transfer via the SRBI, rather than emanating from de novo cholesterol synthesis or decreased esterification.

关 键 词：胆固醇结石 基因表达 载脂蛋白类 脂质累积病 分子生物学 

分 类 号：R575.62[医药卫生—消化系统]