Jiang Zhao-Yan, Parini Paolo, Eggertsen Gösta, Davis Matthew A, Hu Hai, Suo Guang-Jun, Zhang Sheng-Dao, Rudel Lawrence L, Han Tian-Quan, Einarsson Curt
Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute of Digestive Surgery, 200025 Shanghai, China.
J Lipid Res. 2008 Feb;49(2):464-72. doi: 10.1194/jlr.M700295-JLR200. Epub 2007 Nov 15.
Cholesterol supersaturation of bile is one prerequisite for gallstone formation. In the present study of Chinese patients with gallstones, we investigated whether this phenomenon was correlated with the hepatic expression of genes participating in the metabolism of cholesterol and bile acids. Twenty-two nonobese, normolipidemic patients (female-male, 11:11) with gallstones were investigated with 13 age- and body mass index-matched gallstone-free controls (female-male, 10:3). The bile from the gallstone patients had higher cholesterol saturation than that from the controls. The mRNA levels of ABCG5, ABCG8, and liver X receptor alpha (LXRalpha) in the gallstone patients were increased by 51, 59, and 102%, respectively, and significantly correlated with the molar percentage of biliary cholesterol and cholesterol saturation index (CSI). The mRNA and protein levels of the hepatic scavenger receptor class B type I (SR-BI) were increased, and a significant correlation was found between the protein levels and the CSI. No differences were recorded between the two groups concerning the hepatic synthesis of cholesterol, bile acids, and esterification of cholesterol. Our results suggest that the upregulation of ABCG5/ABCG8 in gallstone patients, possibly mediated by increased LXRalpha, may contribute to the cholesterol supersaturation of bile. Our data are consistent with the possibility that increased amounts of biliary cholesterol may originate from plasma HDL cholesterol by enhanced transfer via SR-BI.
胆汁胆固醇过饱和是胆结石形成的一个前提条件。在本次针对中国胆结石患者的研究中，我们调查了这种现象是否与参与胆固醇和胆汁酸代谢的基因的肝脏表达相关。对22名非肥胖、血脂正常的胆结石患者（女∶男 = 11∶11）以及13名年龄和体重指数匹配的无胆结石对照者（女∶男 = 10∶3）进行了研究。胆结石患者的胆汁胆固醇饱和度高于对照组。胆结石患者中ABCG5、ABCG8和肝脏X受体α（LXRα）的mRNA水平分别升高了51%、59%和102%，并且与胆汁胆固醇的摩尔百分比和胆固醇饱和指数（CSI）显著相关。肝脏I型清道夫受体（SR - BI）的mRNA和蛋白质水平升高，并且在蛋白质水平与CSI之间发现显著相关性。两组在胆固醇的肝脏合成、胆汁酸以及胆固醇酯化方面未记录到差异。我们的结果表明，胆结石患者中ABCG5/ABCG8的上调可能由LXRα增加介导，这可能导致胆汁胆固醇过饱和。我们的数据与胆汁中胆固醇量增加可能源于通过SR - BI增强转运的血浆高密度脂蛋白胆固醇这一可能性一致。
