Megalin基因在胆固醇结石病患者胆囊黏膜中的表达及调控  

Expression and regulation of megalin in gallbladder mucosa associated with cholesterol gallstone disease

作　　者：王勇[1] 刘颖斌[1] 蒋兆彦[2,3] 蔡劬[2,3] 姜志宏[2,3] 韩天权[2,3] 张圣道[2,3] 

机构地区：[1]浙江大学医学院附属第二医院外科,杭州310009 [2]上海交通大学医学院附属瑞金医院外科 [3]上海消化外科研究所

出　　处：《中华医学杂志》2009年第16期1110-1113,共4页National Medical Journal of China

基　　金：国家自然科学基金（30672042）;上海交通大学医学院博士点建设基金（BXJ0614）作者单位：（王勇、刘颖斌）;（蒋兆彦、蔡劬、姜志宏、韩天权、张圣道）

摘　　要：目的探讨Megalin基因在胆囊黏膜中的表达和调控与胆固醇结石病的关系。方法采集29例胆囊胆固醇结石病患者和12例无胆石对照患者的胆囊黏膜、囊壁、胆汁、胆石。测定胆石、胆汁脂质，实时PCR检测胆囊黏膜Megalin、Cubilin基因的表达。在胆囊癌细胞株GBC-SD培养液中，分别给予核受体激动剂T0901317、9-顺维甲酸、鹅脱氧胆酸，检测Megalin、Cubilin基因的差异表达。结果胆汁胆固醇摩尔百分比和饱和指数显著高于对照组[（7．98±0．44）mol％比（4．87±0．39）mol％，P〈0．01]，胆石组中Megalin的mRNA表达（17．27％±3．15％）显著高于对照组（5．84％±1．25％，P〈0．05）。Cubilin的表达在两组间差异没有统计学意义。体外给予法尼醇X受体（FXR）的激动剂鹅脱氧胆酸能够诱导Megalin表达的显著上调。结论胆固醇结石病的胆囊黏膜Megalin基因表达增强，有利于胆囊对胆固醇的吸收；Megalin的表达可能受到法尼醇X受体的调控。Objective To explore the relationship between expression and regulation of megalin in gallbladder mucosa and cholesterol gallstone disease. Methods Gallbladder mucosa, gallbladder wall, bile and gallstone were collected from 29 patients with cholesterol gallstone disease （GS） and 12 patients with gallstone free （GSF）. Lipids of bile and stone were measured by kits. Expression of megalin and cubilin was analyzed by real-time PCR. GBC-SD cell line was treated with T0901317, 9-cis ratinoic acid, chenodeoxycholic acid （CDCA） and agunists of LXR, RXR, FXR respectively. Gene expressions were detected. Results Biliary cholesterol % molar and CSI increased significantly in GS group [ （7.98 ± 0. 44） mol% vs（4. 87 ±0. 39 ）mol% ,P 〈0. 01 ]. Megalin expression in GS group was significantly higher than that in GSF group （ P 〈 0. 05 ） and cubilin expression was similar between two groups. In vitro experiments showed that CDCA markedly increased the expression of megalin. Conclusions The increased expression of megalin may help to increase cholesterol uptake in gallbladder and play a compensative role in GS. FXR may participate in the transcriptional regulation of megalin.

关 键 词：基因表达 胆结石 MEGALIN 法尼醇X受体 

分 类 号：R686[医药卫生—骨科学]