胆固醇结石病人肝脏SRBI及其转录调节因子LRH-1基因表达的研究

The mRNA expression of hepatic scavenger receptor B type I and liver receptor homologue 1 in Patients with cholesterol gallstone disease

目的:研究胆固醇结石病人BI型清除剂受体(scavengerreceptorBtypeI,SRBI)及其转录调节因子肝脏受体类似物1(liverreceptorhomologue1,LRH-1)的表达,以探讨胆固醇结石发病的机制。方法:对20例胆囊胆固醇结石病人和10例无胆石症对照者测定血清脂质、胆汁成分和计算胆汁胆固醇饱和指数。以实时定量PCR法测定肝脏SRBI和LRH-1mRNA的表达量。结果:胆石组胆石平均胆固醇含量(86.68±5.26)%,均为胆固醇结石。胆石组病人血清高密度脂蛋白(HDL)显著低于对照组[(0.86±0.62)mmol/L比(1.42±0.56)mmol/L,P<0.01]。胆石组胆汁胆固醇在总脂中的摩尔百分比和胆固醇饱和指数显著高于对照组[(7.80±2.06)mol%比(5.26±2.80)mol%,P<0.05]。胆石组SRBI基因mRNA表达量与对照组比较显著增高(2.48±0.44比1.00±0.23,P<0.05),胆石组LRH-1表达也高于对照组(2.05±0.29比1.00±0.28,P<0.05)。结论:胆固醇结石病的主要病理生理异常为胆汁胆固醇过饱和。肝脏LRH-1、SRBI表达增高,参与了胆固醇过饱和胆汁形成,并促进了胆固醇结石形成。

Objective To study the mRNA expression of hepatic scavenger receptor B type I （SRBI） and liver receptor homologue 1 （LRH-1） in patients with cholesterol gallstone disease, and to elucidate the bio-molecular pathogenesis of gallstone formation. Methods Twenty patients with cholesterol gallstone （CGS, 10 males and 10 females） and 10 controls without gallstones （5 males and 5 females） were enrolled into this study. The mRNA expression of SRBI and LRH-1 were quantified by real-time PCR. Simultaneously, serum lipids and biliary composition were assayed. Cholesterol saturation index （CSI） in bile was calculated. Results Serum high-density lipoprotein （HDL） was significantly lower in CGS than in the controls [（0.86±0.62） mmol/L vs （1.42 ± 0.56） mmol/L, P〈0.05]. In contrast, biliary cholesterol and CSI were significantly elevated in CGS than in the controls [cholesterol： （7.80±2.06） mol% vs （5.26±2.80） mol%, P〈0.01 and CSI： 1.14±0.28 vs 0.741±0.31, P〈0.001]. SRBI and LRH-1 were also expressed higher in CGS patients than in the controls （SRBI： 2.481±0.44 vs 1.00±0.23, P〈0.05; LRH-1： 2.051±0.29 vs 1.00±0.28,P〈0.05）. Conclusion Elevated hepatic LRH-1 and SRBI expressions are closely related with superaturation of biliary cholesterol, which, in turn, contributes to the formation of CGS.