微囊蛋白-1在胆囊结石模型小鼠肝脏胆囊中的表达及意义

Expression and its significance of caveolin-1 in liver and gallbladder of gallstone mice model

目的 探讨微囊蛋白-1在致石饲料诱导的小鼠胆囊胆固醇结石症形成中的作用及其可能的机制.方法 以结石易感C57BL/6小鼠为研究对象,分别给予对照组共6只和实验组共6只小鼠普通饲料和致石饲料饲养4周,检测小鼠胆囊胆固醇结石形成状况、血脂、胆汁脂质含量变化.采用实时定量PCR法和Western蛋白印迹法检测小鼠肝脏及胆囊组织中微囊蛋白-1、清道夫受体B族Ⅰ型（SR-BI）的mRNA和蛋白表达水平和变化.采用t检验比较两组均数.结果 致石饲料饲养后4周,实验组小鼠胆囊成石率为100％,血脂水平明显升高;胆汁中胆固醇成分明显增加,胆盐减少.与对照组相比,微囊蛋白1在实验组小鼠肝脏和胆囊组织中mRNA和蛋白水平表达均显著下调（肝脏mRNA相对定量值为0.53±0.13比1.00±0.32,t=3.330;蛋白相对定量值为0.39±0.07比0.92±0.06,t=10.280;胆囊mRNA相对定量值为0.40±0.22比1.00±0.22,t=3.823;蛋白相对定量值为1.04±0.07比1.34±0.04,t=6.367,P均＜0.01）.实验组小鼠肝胆组织的SR-BⅠ蛋白和mRNA相对定量与对照组相比差异均无统计学意义（P均＞0.05）.结论 肝胆组织中微囊蛋白-1的mRNA和蛋白表达水平变化可能影响实验小鼠肝胆组织中的脂质代谢和胆固醇转运,在胆囊胆固醇结石的形成中发挥着作用.

Objective To investigate the role and possible mechanism of caveolin-1 （CAV1） in the forming of cholesterol gallstone in mice fed with lithogenic diet.Methods Cholesterol gallstone susceptible C57BL/6 mice were study objects.The mice of control group （n=6） and experiment group （n=6） were fed with normal diet and lithogenic diet for four weeks respectively.The condition of cholesterol gallstone forming,changes of serum lipid and bile composition were measured,and the expressions of CAV1 and scavenger receptor classB member Ⅰ （SR-BⅠ） at mRNA and protein level in the liver and gallbladder were detected by realtime-polymerase chain reaction and Western blot,respectively.The t test was performed for mean comparsion between the two groups.Results The incidence rate of gallstone in experimental group was 100% after fed with lithogenic diet for four weeks,the lipid level significantly increased,and the proportion of cholesterol in bile raised and bile salt decreased.Compared with those of control group,the expressions of CAV1 at mRNA and protein level in the liver and gallbladder tissues siginificantly decreased （in liver tissue,mRNA 0.53 ± 0.13 vs 1.00 ± 0.32,t =3.330,protein level 0.39 ± 0.07vs 0.92±0.06,t=10.280; in gallbladder tissue,mRNA 0.40±0.22 vs 1.00±0.22,t=3.823,protein level 1.04±0.07 vs 1.34 ± 0.04,t =6.367,all P〈0.01）.There was no significant difference in the relative expression of SR-BⅠ at mRNA and protein level in the liver and gallbladder tissues between the mice of experiment group and control group.Conclusion The changes of CAV 1 expression at mRNA and protein level in liver and gallbladder tissues may affect lipids metabolism and cholesterol transportation in liver and gallbladder tissues of experiment mice,which might play an important role in the formation of cholesterol gallstone.