回肠Na+/胆汁酸转运体抑制剂SC-435对豚鼠胃肠移行性复合波的作用

摘要

目的:研究回肠Na+/胆酸转运体( IBAT)抑制剂SC-435喂养后,豚鼠胃肠移行性复合波(MMC)与胆酸池大小的变化.方法:60只豚鼠分别给予正常饮食和IBAT抑制剂SC-435饮食2周、4周、8周.喂养结束后,评估胆囊动力并将4对电极植入胃窦、12指肠、空肠、回肠.7 d后,记录MMC并测量胆酸池大小.结果:IBAT抑制剂喂养后,胆囊动力在4周与8周组下降.胆酸池在4周组减小17.11% (P<0.05),8周组减小48.35%(P<0.05).MMC起源部位发生改变:胃窦起源(37%)和十二指肠起源(46%)减少而空肠起源(17%)增多.与对照组相比,MMC周期延长(4周组1.16倍,P<0.05; 8周组1.38倍,P<0.05)而波幅降低 (4周组降低10.58%,P<0.05; 8周组降低49.17 %,P<0.05).在对照组与2周组之间,所有MMC参数无统计学意义差异.结论:IBAT抑制剂 SC-435减小胆酸池并抑制MMC运动; MMC与胆酸肠肝循环有关,与胆酸池大小改变一致.%Objective To determine whether SC-435, a new ileal apical sodium-codependent bile acid transporter (IBAT) inhibitor, can alter the gastrointestinal motility in guinea pigs. Methods Sixty guinea pigs received regular diet or IBAT inhibitor (SC-435) diet for 2, 4, and 8 weeks, respectively. At the end of the feeding period, the gallbladder motility was assessed and then four bipolar silver electrodes were implanted on the antrum, duodenum, jejunum, and ileum. Seven days later, migrating motor complex (MMC) was recorded and the total bile acid pool size was measured according to the isotope dilution principle in the meantime. Results After feeding SC-435, the gallbla-dder motility was declined in the 4-week group and the 8-week group. The bile acid pool size decreased by 17.11% (P<0.05) in the 4-week group and 48.35% (P<0.05) in the 8-week group. The places of origin of MMC were changed where antral origins (37%) and duodenal origins (46%) decreased whereas jejunal origins (17%) increased. The MMC cycle period was prolonged in the duodenum (1.16 times in the 4-week group, P< 0.05; 1.38 times in the 8-week group, P<0.05) whereas MMC amplitude fell in the duodenum (10.58% in the 4-week group, P<0.05; 49.17% in the 8-week group, P<0.05). There were not significant differences in all parameters of MMC between the control group and the 2-week group in guinea pigs. Conclusion The IBAT inhibitor (SC-435) reduces the bile acid pool size and inhibits the MMC cycle activity. MMC is related to the enterohepatic circulation of bile acids, which is consistent with the changes of the bile acid pool size in guinea pigs.