胆固醇结石患者肝脏核受体基因表达的研究

mRNA Expression of Liver Nuclear Receptor Genes in Patients with Cholesterol Gallstone Disease

目的研究胆囊胆固醇结石患者肝脏的核受体基因:肝脏X受体α(liver X receptor α,LXRα)、法尼醇受体(farnesoid X receptor,FXR)、人类固醇异生物受体(steroid xenobiotic receptor,SXR)及肝受体同类物1(liver receptor homolog 1,LRH-1)的表达,探讨胆固醇结石病的发病机理。方法27例胆囊胆固醇结石患者(胆石组),男6例,女21例,平均年龄(52.44±1.92)岁。10例无胆石症的胆囊息肉患者为对照(对照组),男6例,女4例,平均年龄(47.10±2.73)岁。测定胆石胆固醇成分及血清脂类成分:总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-ch)、载脂蛋白(Apo)B和ApoA1和胆汁脂类成分(胆固醇、磷脂和胆汁酸),并计算胆汁总脂和胆汁胆固醇饱和指数。实时定量PCR法测定肝脏LRH-1、FXR、SXR及LXRα基因的表达量。结果胆石组血清中HDL-ch浓度明显低于对照组〔(0.93±0.05)mmol/L vs(1.33±0.09)mmol/L〕,P<0.001;ApoA1浓度也低于对照组〔(1.19±0.05)g/L vs(1.36±0.06)g/L〕,P<0.05;血清ApoB、TC和TG2组比较差异均无统计学意义(P>0.05)。胆石组胆汁呈胆固醇过饱和(胆固醇过饱和指数:1.17±0.02 vs 0.79±0.10,P<0.001);胆汁胆固醇摩尔百分比浓度较对照组升高〔(7.96±0.39)mol% vs(5.26±0.89)mol%〕,P<0.01;胆汁总脂较对照组明显下降〔(104.72±10.51)g/L vs(154.24±14.20)g/L〕,P<0.05;胆汁中胆汁酸和磷脂成分2组比较差异均无统计学意义(P>0.05)。胆石组LRH-1表达高于对照组(14.18±1.80 vs 7.22±2.22),P<0.05,LXRα、FXR和SXR表达2组差异无统计学意义(P>0.05)。结论人类肝脏LRH-1的表达增高与胆囊胆固醇结石形成有关。

Objective To investigate the mRNA expressions of liver X receptor α （LXRα）, farnesoid X recep tor （FXR）, steroid xenobiotic receptor （SXR） and liver receptor homolog 1 （LRH-1） gene in patients with cholesterol gallstone （CGS） disease in order to elucidate the biomolecular pathogenesis of gallstone formation. Methods Twenty-seven patients with CGS （CGS group） and 10 controls without gallstones （control group） were included in this study. Serum lipid composition （total cholesterol, triglyceride, high density lipoprotein cholesterol, apoprotein B, apoprotein A1）, gallstone cholesterol concentration and biliary composition （cholesterol, bile salts, lecithin） were assayed. Biliary total lipid and cholesterol saturation index （CSI） were calculated, mRNA expressions of LRH-1, FXR, SXR and LXRα gene were determined by real-time polymorphism chain reaction. Results Serum high density lipoprotein cholesterol concentration was lower in CGS group than that in control group [（0.93±0.05） mmol/L vs （1.33±0.09） mmol/L, P〈0. 001] and serum apoprotein A1 was also lower in CGS group than that in control group [（1.19±0.05） g/L vs （1.36±0.06） g/L, P〈0.05]. There were no differences in serum total cho lesterol, triglyceride and apoprotein B between two groups （P〉0.05）. CSI was higher in CGS group than that in control group （1.17±0.02 vs 0.79±0.10）, P〈0.001. Biliary cholesterol was also higher in CGS group than that in control group [（7.96±0.39） mol% vs （5.26±0.89） mol%, P〈0.011, while biliary total lipid was lower in CGS group than that in control group [（104. 72±10. 51） g/L vs （154.24±14.20） g/L, P〈0. 05]. There were no differences in bile salts and lecithin between two groups （P〉0. 05）. Expression of LRH-1 gene was higher in CGS group than that in control group （14. 18 ± 1. 80 vs 7. 22 ± 2. 22）, the difference was statistically significant （P〈0.05）. There were no differences in mRNA expressions of LXRα, FXR and SXR gene between two groups （P〉0.05）. Conclusion CGS disease may be related to increased expression of LRH-1 gene.