药物诱导胆红素葡萄糖醛酸转移酶的基因表达对小鼠胆结石形成的抑制作用  

The inhibiting effect on the gallstone formation by drug induced bilirubin UDP glucuronosyltransferase gene expression

作　　者：张红军[1] 祝学光[1] 陈祥柏[1] 赵华[1] 赵娜 

机构地区：[1]北京医科大学人民医院普通外科,100044

出　　处：《中华普通外科杂志》1999年第5期344-347,共4页Chinese Journal of General Surgery

基　　金：国家自然科学基金

摘　　要：目的　通过药物诱导肝脏胆红素尿苷二磷酸葡萄糖醛酸转移酶（ Ｂ Ｕ Ｇ Ｔ） 基因表达，观察其对胆固醇结石形成的抑制作用。 方法　对３ 组 Ｃ５７ Ｂ Ｌ／６ 小鼠５０ 只分别予正常商品饲料（ 对照组， Ｎ 组）１０ 只，致石饮食（ 胆石组， Ｇ 组）２０ 只，另一组在致石饮食中加００５ ％ 苯巴比妥（ 苯巴比妥组， Ｐ 组）２０ 只，６ 周后观察结石形成率，检测结石中胆固醇沉淀量，比较肝脏 Ｂ Ｕ Ｇ Ｔ活性及其基因ｍ Ｒ Ｎ Ａ水平的表达、胆汁中胆红素成份、血脂变化。 结果　 Ｐ 组与 Ｇ 组胆结石形成率差别不显著，但 Ｐ 组比 Ｇ 组小鼠胆结石中胆固醇沉淀量显著减少（ Ｐ＜ ００１） ；３ 组中 Ｇ 组小鼠肝脏 Ｂ Ｕ Ｇ Ｔ 活性及基因ｍ Ｒ Ｎ Ａ水平的表达均最低， Ｎ 组肝脏 Ｂ Ｕ Ｇ Ｔ活性最高， Ｐ 组肝脏 Ｂ Ｕ Ｇ Ｔ 基因表达ｍ Ｒ Ｎ Ａ 水平最高； Ｇ 组小鼠胆汁中单结合胆红素（ Ｍ Ｃ Ｂ） 占总胆红素的比例在３ 组中最高，而 Ｎ 组最低 结论　致石饮食通过某些机制抑制了肝脏 Ｂ Ｕ Ｇ Ｔ 的活性和基因表达，致使胆红素葡萄糖醛酸化障碍，胆汁中 Ｍ Ｃ Ｂ增多，促进了胆固醇结石的形成，苯巴比妥能诱导肝脏 Ｂ Ｕ Ｇ Ｔ 基因的表达，使 Ｂ Ｕ Ｇ Ｔ活性升高?Objective To observe the inhibiting effect on cholesterol gallstone formation by drug induced hepatic bilirubin UDP glucuronosyltrasferase (B UGT) gene expression. Methods Fivety C57BL/6 mice were devided into three groups fed with normal fodder (N group), lithogenic chaw (G group) and lithogenic chaw added by 0.05% phenobarbital (P group) respectively. 6 weeks later, the rates of gallstone formation were observed, and the amount of precipitated cholesterol in gallstones was detected. The activity of hepatic B UGT, the expression of hepatic B UGT gene, bilirubin in bile and blood lipids were measured and compared among three groups. Results There was no significant difference in the rate of gallstone formation between P and G group, but the content of cholesterol in the gallstones of P group was less than that in G group ( P <0.01). The activities of hepatic B UGT and the mRNA expression of hepatic B UGT gene in G group were the lowest among three groups.The activity of hepatic B UGT in N group and mRNA expression of hepatic B UGT gene in P group was the highest. The ratio of monoconjugated bilirubin over total bilirubin in bile (MCB/TB) was the highest in G group and the lowest in N group. Conclusion The lithogenic chaw inhibits the activity of hepatic B UGT and the mRNA expression of hepatic B UGT gene by way of abnormal bilirubin glucuronidation and elevated biliary MCB/TB ratio contributes to the cholesterol gallstone formation.Phenobarbital may inhibit the cholesterol gallstone formation to some extent.

关 键 词：胆结石 胆红素 动物实验 B-UGT 

分 类 号：R657.42[医药卫生—外科学]