目的 通过激活小鼠肝脏X受体,观察胆汁脂质成分变化与胆固醇代谢相关基因的表达情况,观察肝脏X受体在胆石病发生中的作用。方法 C57BL小鼠18只,分为2组,分别管饲肝脏X受体激动剂T0901317和安慰剂。分析胆汁脂质成分。实时定量PCR法测定肝脏与腹腔巨噬细胞的胆固醇代谢相关基因mRNA表达量。结果 实验组胆汁胆固醇摩尔百分比较对照组升高89%。实验组肝脏组织Abcg5、Abcg8、Abcal与Srebpl表达显著高于对照组:Abc茚为2.96±0.55比1.10±0.22(P〈0.01);Abcg8为0.86±0.16比0.29±0.07(P〈0.01);Abcal为8.45±1.06±5.51±0.84(P〈0.05);Srebpl为14.08±3.18比3.06±0.74(P〈0.01)。腹腔巨噬细胞Abcal表达实验组高于对照组(27.66±7.18比8.39±3.65,P〈0.05)。结论 肝脏X受体激活使胆固醇逆转运增强,肝脏摄取的过多胆固醇通过胆汁清除,导致胆汁胆固醇含量升高,提示肝脏X受体在胆石病发生中有重要作用。
Objective To study the changes of the biliary lipids composition and the expression of genes related to cholesterol metabolism in mice upon activation of liver X receptors. Methods Eighteen C57BL mice were divided into experimental group and control group randomly. Experimental group received T0901317 by gavage for 5 days. And control group was treated with the solvent only. Biliary lipids composition was measured. The mRNA expression levels of genes in liver and macrophages were analyzed by real-time PCR. Results The molar percent of biliary cholesterol was increased by 89% in experimental group as compared with control group. T0901317 treatment elevated the expression levels of Abcg5, Abcg8,Abcal and Srebpl significantly in liver (experimental group vs control: AbcgS,2.96 ± 0.55 vs 1.10±0.22,P 〈0.01 ; AbcgS,0.86 ±0.16 vs 0.29 ±0.07,P 〈0.01; Abcal,8.45 ± 1.06 vs 5.51 ± 0.84,P 〈 0.05 ; Srebpl, 14.08 ± 3. 18 vs 3.06 ± 0.74, P 〈 0.01 ). The expression levels of Abcal in macrophages were increased significantly in experimental group as compared with control group (27.66 ± 7.18 vs 8.39 ± 3.65,P 〈 0.05). Conclusion Reverse cholesterol transport was enhanced from peripheral ceils to liver upon activation of liver X receptors. Excess cholesterol in liver was eliminated by secretion into bile. These processes caused elevation of cholesterol content in bile. The results highlight the role of liver X receptors in the pathogenesis of gallstone formation.