核受体基因在家族遗传性胆囊胆固醇结石患者肝组织中表达的变化

Changes in expressions of nuclear receptor genes in liver tissue of patients with hereditary cholesterol gallstone

目的:探讨核受体(NRs)基因在汉族人群中家族遗传性胆囊胆固醇结石(HCGD)患者肝组织中表达的变化。方法:收集9例HCGD患者(HCGD组)、9例散发性胆固醇结石患者(SCGD,SCGD组)和7例无胆石病肝血管瘤患者(对照组)血液与手术肝组织标本。用酶法检测血清脂代谢相关指标,用qRT-PCR测定肝组织肝NRs:肝X受体(LXRα)、法尼醇X受体(FXR)、甾醇调节元件结合蛋白2(SREBP2)、雌激素受体α/β(ERα/β)、G蛋白偶联受体30(GPR30)、过氧化物酶体增殖物激活受体γ(PPARγ)mRNA的表达。结果:HCGD组血清总胆汁酸(TBA)含量较对照组与SCGD组明显降低(均P<0.05),其余脂代谢相关指标各组间均无统计学差异(均P>0.05)。与对照组比较,HCGD组ERα/β、SREBP2、PPARγ的mRNA表达量明显升高,SCGD组FXRmRNA明显升高(均P<0.05);LXRα和GPR30mRNA在各组间均无统计学差异(均P>0.05)。HCGD组中ERα、ERβmRNA表达与患者血清TBA水平呈负相关(r=-1.000,P=0.000;r=-0.989,P=0.011)。结论:ERα/β、SREBP2、PPARγ基因在HCGD患者肝组织中表达上调,其高表达可能参与了HCGD的发生发展。

Objective:To investigate the changes in gene expressions of nuclear receptors(NRs)in hepatic tissue of patients with hereditary cholesterol gallstone(HCGD)of Chinese Han nationality.Methods:The blood samples and surgical specimens of hepatic tissue from 9 patients with HCGD(HCGD group),9 patients with sporadic cholesterol gallstone(SCGD,SCGD group),and 7 hepatic hemangioma patients without gallstone(control group)were collected.The serum levels of lipid metabolism related indicators were determined by enzymatic assay,and mRNA expressions of NRs in liver tissues,which included liver X receptor(LXRα),farnesoid X receptor(FXR),sterol regulatory element binding protein 2(SREBP2),estrogen receptorsαandβ(ERα/β),G protein-coupled receptor 30(GPR30),peroxisome proliferator activated receptorγ(PPARγ),were examined by qRT-PCR.Results:The serum level of total bile acid(TBA)in HCGD group was significantly reduced compared with control group and SCGD group(both P<0.05),while no significant differences were noted in other lipid metabolism related indicators among the three groups(all P>0.05).Compared with control group,the mRNA expression levels of ERα/β,SREBP2,and PPARγin HCGD group were significantly increased in HCGD group,and the FXR mRNA expression level was significantly increased in SCGD group(all P<0.05);the mRNA expression levels of LXRαand GPR30 showed no significant differences among the three groups(both P>0.05).in HCGD group,the mRNA expressions of ERαand ERβwere negatively correlated with the serum TBA level(r=–1.000,P=0.000;r=–0.989,P=0.011).Conclusion:The genes expressions of ERα/β,SREBP2 and PPARγare up-regulated in the liver tissue of HCGD patients,which may play important roles in the pathogenesis of HCGD.