Cohen M B, Nogueira J, Laney D W, Conti T R
Division of Pediatric Gastroenterology and Nutrition, Children's Hospital Research Foundation, Cincinnati, Ohio.
Pediatr Res. 1992 Mar;31(3):228-33. doi: 10.1203/00006450-199203000-00007.
Undernutrition in human infants is associated with more prolonged episodes of diarrheal disease. Therefore, we tested the hypothesis that malnutrition prolongs the duration of Escherichia coli heat-stable enterotoxin-induced rat jejunal secretion. At weaning, rats were separated into two groups: malnourished rats were fed 50% of the previous day's intake of the fully fed control group. After approximately 2 wk of pair feeding, when malnourished rats weighed less than or equal to 60% of the full fed control group, we measured the secretory response to heat-stable enterotoxin in ligated jejunal loops. Toxin-induced secretion was equal in both groups until 30 min incubation time, after which net secretion continued to increase in the malnourished group but decreased in the fully fed group. Jejunal brush border membranes prepared from malnourished and fully fed rats demonstrated similar heat-stable enterotoxin receptor density, avidity of binding and guanyl cyclase activation. In both groups, radiolabeled toxin injected into in situ jejunal loops was converted into an altered radioligand unable to bind to brush border membranes. However, in malnourished rats, there was both increased appearance of two additional radioligands that still retained their ability to bind to brush border membranes and persistence of biologically active unlabeled toxin as measured in the suckling mouse bioassay. Our studies demonstrate that reduced or delayed inactivation of heat-stable enterotoxin, with continued presence of active toxin species, may contribute to prolonged secretion in the jejunum of malnourished rats.
人类婴儿营养不良与腹泻病发作时间延长有关。因此，我们检验了以下假说：营养不良会延长大肠杆菌热稳定肠毒素诱导的大鼠空肠分泌持续时间。在断奶时，将大鼠分为两组：营养不良组大鼠的喂食量为前一天全量喂食对照组摄入量的50%。经过约2周的配对喂食后，当营养不良组大鼠体重小于或等于全量喂食对照组的60%时，我们测量了结扎空肠袢对热稳定肠毒素的分泌反应。在孵育30分钟前，两组毒素诱导的分泌量相等，在此之后，营养不良组的净分泌量持续增加，而全量喂食组的净分泌量减少。从营养不良组和全量喂食组大鼠制备的空肠刷状缘膜显示出相似的热稳定肠毒素受体密度、结合亲和力和鸟苷酸环化酶激活情况。在两组中，注入原位空肠袢的放射性标记毒素均转化为一种改变的放射性配体，无法与刷状缘膜结合。然而，在营养不良的大鼠中，出现了另外两种仍保留与刷状缘膜结合能力的放射性配体，并且在乳鼠生物测定中测得生物活性未标记毒素持续存在。我们的研究表明，热稳定肠毒素的失活减少或延迟，以及活性毒素种类的持续存在，可能导致营养不良大鼠空肠分泌延长。
