氨肽酶N的表达及其与结石形成的关系(英文)

 为研究大鼠高胆固醇饮食时 ,肝脏氨肽酶N(APN)在实验结石形成中可能的结石发生作用 ,采用 1.2 %胆固醇饮食 4周 ,诱发新西兰兔胆囊结石形成 .根据兔APN基因cDNA序列设计引物 ,提取肝脏总RNA .利用RT PCR检测肝脏APNmRNA水平的变化 ,用组织化学方法观察肝脏毛细胆管膜上APN的表达 .观察新西兰兔胆囊结石形成过程中肝脏APN的mRNA水平的变化、APN表达及胆汁中APN活性、胆脂、总蛋白含量的变化 ,探讨APN在胆石形成中可能的作用 .经成石饲料饲养后 ,随着胆汁饱和度增加和APN活性加强 ,胆囊结石组肝脏APNmRNA水平较对照组明显增高 ,胆囊结石组胆汁中总胆固醇、CSI、总蛋白浓度及APN活性均明显高于对照组 ,且胆汁中APN活性与肝脏APN的表达及胆汁CSI增高呈正相关 .结果提示 ,当存在胆汁过饱和的情况下 ,APN很可能作为促成核因子在胆结石形成早期发挥重要作用

Expression of Aminopeptidase N and Its Correlation with the Gallstones Formation

The aim was to explore the possible lithogenic role of aminopeptidase N (APN) in experimental gallstone formation in rabbits with high cholesterol diet.The mRNA level and the expression of APN in liver tissue and its dynamic enzymatic activities as well as the concentration of biliary lipids, protein in bile were measured and compared with those rabbits with normal diet, gallstones were induced by 1.2% high cholesterol lithogenic diet in 10 New Zealand rabbits for 10 days and another 10 rabbits for 4 weeks compared with the control group(with normal rabbits chow).Expression of APN gene and APN protein in liver tissue were measured by RT PCR and histochemical techniques respectively. During the development of the experimental gallstones, the expression of APN gene and APN protein in liver tissue were simultaneously elevated with the increase of biliary cholesterol saturation, and significantly higher than that of the control group.The enzymatic activity of APN in bile was also significantly higher than that of the control group. A positive correlation was found between the biliary APN activity and hepatic APN expression and biliary cholesterol saturation index ( CSI ).The results suggested that APN, as a potent pronucleating factor, might play a critical role in the early stage of the pathogenesis of gallstone disease when the bile was saturated with cholesterol.