Bhatia A M, Ramos C T, Scott S M, Musemeche C A
Department of Surgery, University of New Mexico School of Medicine, Albuquerque, USA.
J Invest Surg. 1996 Sep-Oct;9(5):351-8. doi: 10.3109/08941939609021276.
Platelet-activating factor (PAF) is an important endogenous mediator of neonatal necrotizing enterocolitis (NEC). Injection of PAF into weanling and adult rats causes ischemic bowel necrosis that is morphologically similar to NEC. The purpose of this study was to adapt the PAF model of intestinal injury to the suckling rat and to attempt to alter susceptibility to PAF-induced bowel necrosis by early weaning and formula feeds. At ages 15 to 20 days, rat pups were selected to be weaned to either formula or 5% dextrose or to nurse ad lib (total n = 54). At ages 16, 18, 20, 21, 23, or 25 days of life, animals received PAF (50 micrograms/kg) and endotoxin (1 mg/kg) by intraperitoneal injection. Animals were sacrificed 2 h after injection. Intestinal samples were submitted to be graded by a pathologist in a blinded fashion. Injury scores ranged from 0 to 10, based on the percentage of villous necrosis. Prior to age 20 days, minimal histologic injury was present (mean scores on days 16, 18 = 1.7 +/- 0.9, 1.7 +/- 0.6). Combined injury scores for weaned and nursed animals on days 20 and 23 were significantly greater than on days 16 and 18 (p = .0001). Histologic injury in the dextrose group was significantly less than the formula-fed group on day 21 and greater on day 25. Suckling rats showed resistance to PAF-induced bowel necrosis prior to 20 days of age, during the middle of the weaning period. Early weaning to formula did not alter susceptibility to injury, which suggests that PAF-acetylhydrolase from breast milk does not confer this resistance to PAF.
血小板活化因子（PAF）是新生儿坏死性小肠结肠炎（NEC）的一种重要内源性介质。向断奶幼鼠和成年大鼠注射PAF会导致缺血性肠坏死，其形态与NEC相似。本研究的目的是使PAF肠道损伤模型适用于乳鼠，并试图通过早期断奶和配方奶喂养来改变对PAF诱导的肠坏死的易感性。在15至20日龄时，选择幼鼠断奶，改为喂食配方奶或5%葡萄糖，或自由哺乳（总数n = 54）。在16、18、20、21、23或25日龄时，通过腹腔注射给予动物PAF（50微克/千克）和内毒素（1毫克/千克）。注射后2小时处死动物。肠道样本由病理学家以盲法进行分级。损伤评分根据绒毛坏死百分比在0至10分之间。在20日龄之前，组织学损伤最小（16、18日龄时的平均评分为1.7 +/- 0.9、1.7 +/- 0.6）。断奶和哺乳动物在20日龄和23日龄时的联合损伤评分显著高于16日龄和18日龄时（p = .0001）。葡萄糖组在21日龄时的组织学损伤明显小于配方奶喂养组，在25日龄时则更大。乳鼠在20日龄之前，即断奶期中期，对PAF诱导的肠坏死具有抵抗力。早期断奶改为配方奶喂养并未改变对损伤的易感性，这表明母乳中的PAF - 乙酰水解酶并未赋予对PAF的这种抵抗力。
