Smale Simon, Bjarnason Ingvar
Department of Gastroenterology, Guy's, King's, St Thomas' Medical School, Bessemer Road, London, UK.
Br J Clin Pharmacol. 2003 Sep;56(3):284-91. doi: 10.1046/j.1365-2125.2003.01942.x.
Intestinal integrity is maintained by a delicate balance between mucosal defence and luminal aggressors that cause damage if exposed to the mucosa. The intestinal barrier function appears to be the gatekeeper for controlling this balance. It is becoming increasingly clear that if the intestinal barrier is disrupted the consequences are low grade intestinal inflammation which carry with it the risk of significant blood and protein loss both of which may cause clinical management problems. We review the strength and weaknesses of methods for assessing small bowel function that are useful for assessing drug-induced intestinal toxicity. There are a number of imaging methods for assessing intestinal integrity but these do not provide functional information. Intestinal permeability measurements have been optimized for specificity and there are now ways of measuring intestinal permeability regionally, but marker analyses continue to be cumbersome. Recent developments of faecal inflammatory markers make it a matter of routine to assess this in any routine chemical pathology laboratory. Bleeding, protein loss and other complications of inflammation can also be measured with good specificity, but again the methods are cumbersome. Using a combination of functional and imaging techniques it is now possible to characterize and define with precision, the small bowel side-effects of drugs, the best example being the small bowel side-effects of nonsteroidal anti-inflammatory drugs (NSAIDs).
肠道完整性通过黏膜防御与管腔侵袭物之间的微妙平衡得以维持,管腔侵袭物若接触到黏膜会造成损伤。肠道屏障功能似乎是控制这种平衡的关键因素。越来越清楚的是,如果肠道屏障被破坏,后果是低度肠道炎症,这伴随着大量血液和蛋白质流失的风险,而这两者都可能导致临床管理问题。我们综述了评估小肠功能的方法的优缺点,这些方法对评估药物诱导的肠道毒性很有用。有多种成像方法可用于评估肠道完整性,但这些方法无法提供功能信息。肠道通透性测量在特异性方面已得到优化,现在有区域测量肠道通透性的方法,但标志物分析仍然繁琐。粪便炎症标志物的最新进展使得在任何常规化学病理实验室进行此项评估成为常规操作。出血、蛋白质流失和炎症的其他并发症也能够以良好的特异性进行测量,但同样,这些方法也很繁琐。通过结合功能和成像技术,现在能够精确地表征和定义药物对小肠的副作用,非甾体抗炎药(NSAIDs)对小肠的副作用就是最好的例子。