熊脱氧胆酸抑制兔胆结石形成的作用及机制  

The mechanism of the inhibitory effect of ursodeoxycholate on gallstone formation in rabbits

作　　者：李月廷[1] 祝学光[1] 陈祥柏[1] 赵昕亮[2] 

机构地区：[1]北京大学人民医院普通外科,北京100044 [2]北京大学基础医学院生物化学与分子生物学系

出　　处：《北京大学学报（医学版）》2001年第5期469-471,共3页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金 ( 39770 719)资助~~

摘　　要：目的 :观察熊脱氧胆酸 (UDCA)对新西兰兔胆囊结石形成、肝氨肽酶N(APN)mRNA水平及胆汁中APN活性和总蛋白含量的影响 ,探讨UDCA预防胆囊结石形成的机制。方法 :(1)动物模型 :新西兰兔 30只。对照组 10只 ,普通饮食 ;结石组 10只 ,喂含 1.2g·d-1胆固醇的成石饮食 4周 ;UDCA组 10只 ,同时喂饲含 1.2g·d-1胆固醇和 0 .0 45 g·d-1的UDCA饮食 4周。 (2 )APN表达 :根据兔APN基因cDNA序列设计引物 ,提取肝总RNA ,利用RT PCR方法 ,检测肝APNmRNA水平的变化。 (3)APN活性 :用化学法检测。 (4 )胆汁中脂类、总蛋白的含量 :用生化方法检测。 (5 )胆固醇饱和指数 (CSI)计算 :用Carey表计算。 结果 :结石组 6只 (6 / 10 )出现胆囊结石 ,9只 (9/10 )出现胆固醇结晶 ,UDCA组和对照组无结石及结晶出现 ;对照组和UDCA组胆囊胆汁中CSI(对照组 0 .80±0 .0 9、结石组 1.38± 0 .2 7及UDCA组 1.18± 0 .11)、总蛋白浓度 (对照组 1.2 5± 0 .49、结石组 4.5 8± 0 .93及UDCA组 3.12± 0 .78)明显低于结石组 (P均小于 0 .0 5 ) ,而结石组APNmRNAIOD比值 (对照组 0 .6 5± 0 .18、结石组1.0 8± 0 .35及UDCA组 0 .72± 0 .2 3)、APN活性 [对照组 (6 .10± 2 .5 3)U·L-1、结石组 (2 3.6 4± 10 .36 )U·L-1及UDCA组 (8.0Objective: To explore the mechanism of the inhibitory effect of ursodeoxycholate(UDCA) on experimental gallstone formation. Methods:3 dietary groups of New Zealand rabbits with 10 each were allocated as control (normal rabbits chow), lithogenic (1.2 g high cholesterol diet) and UDCA prevention (1.2 g high cholesterol diet + 0.045 g·d -1 UDCA) groups respectively for 4 weeks. RT PCR was performed for APN gene expression in liver tissue. The enzymatic activity of APN in biles and the concentrations of biliary lipids and protein were analyzed chemically.Gallbladder biles were collected for determining the presence of cholesterol crystals and gallstones both micro and macroscopically and were qualitatively analyzed by infrared spectroscopy.Results: Compared with the negative results both in control and UDCA preventive groups, cholesterol crystals and stones were found in 9 and 6 out of 10 gallbladders respectively in lithogenic group.The integrated optical density ratio value(IOD) of mRNA for APN gene was much higher in lithogenic group(1.08±0.35) than that of control and UDCA preventive groups (0.65±0.18 and 0.72±0.23 respectively) with the results of the enzymatic activity of APN as (6.10±2.53) U·L -1 , (8.01±2.89) U·L -1 and (23.64±10.36) U·L -1 in control, UDCA preventive and lithogenic groups respectively. Conclusion: UDCA prevents the formation of cholesterol gallstones most likely by inhibiting the lithogenic role of APN.

关 键 词：熊去氧胆酸 药理学 胆固醇 代谢 氨肽酶N 胆结石 预防 控制 

分 类 号：R575.62[医药卫生—消化系统]