Eliakim R, Karmeli F, Cohen P, Rachmilewitz D, Shao J S, Alpers D H
Department of Medicine, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel.
Inflamm Bowel Dis. 1999 Feb;5(1):16-23. doi: 10.1097/00054725-199902000-00003.
A rat model of experimental colitis and jejunitis induced by iodoacetamide (IA), a sulphydryl blocker is accompanied by increased leukotriene, prostaglandin E2 (PGE2) generation, and nitric oxide synthase (NOS) activity. Rat small intestinal and colonic surfactant-like particles (SLP) that accumulate on the apical surface of mucosal cells have been identified and specific antibodies to them have been produced. The aim of this study was to evaluate a possible role of SLP in IA-induced colitis and jejunitis. Inflammation was induced in Sprague-Dawley rats either by intracolonic administration of 3% IA (0.1 ml) or by intrajejunal administration of 2% IA (0.1 ml). Antisera raised against either colonic SLP, pulmonary SP-A (a major protein associated with colonic SLP), or small intestinal SLP were injected into the tail vein of rats 48 h before, simultaneous with, or 24 h after IA administration. Rats were killed 2 or 10 days after IA was given, their colon or small intestine was isolated and rinsed, and a segment of colon (10 cm) or small bowel (30 cm) was weighed and processed for microscopy, NOS and myeloperoxidase (MPO) activities, and PGE2 generation. Intracolonic or jejunal IA resulted after 48 h in extensive macroscopic and microscopic damage, accompanied by increased segmental weight, MPO and NOS activity, and PGE2 generation. Colonic SLP antibody administration, either 48 h before or at the time of damage induction, significantly decreased macroscopic as well as microscopic damage, segmental weight, MPO activity, and PGE2 generation, but had no effect on NOS activity. Neither control sera nor antisera against SP-A had any protective effect, nor did injection of anti-colonic SLP antisera given 24 h after IA. Small bowel SLP antibody offered no protection against IA jejunitis. IA-induced colitis but not jejunitis is ameliorated by intravenous injection of SLP antibody by a mechanism yet to be determined. These data provide further evidence of a physiologic role for gastrointestinal SLP.
由巯基阻断剂碘乙酰胺（IA）诱导的实验性结肠炎和空肠炎大鼠模型伴有白三烯、前列腺素E2（PGE2）生成增加以及一氧化氮合酶（NOS）活性增强。已鉴定出积聚在黏膜细胞顶端表面的大鼠小肠和结肠表面活性样颗粒（SLP），并制备了针对它们的特异性抗体。本研究的目的是评估SLP在IA诱导的结肠炎和空肠炎中可能的作用。通过结肠内注射3% IA（0.1 ml）或空肠内注射2% IA（0.1 ml）在Sprague-Dawley大鼠中诱导炎症。在IA给药前48小时、同时或给药后24小时，将针对结肠SLP、肺表面活性蛋白A（SP-A，一种与结肠SLP相关的主要蛋白质）或小肠SLP产生的抗血清注入大鼠尾静脉。在给予IA后2天或10天处死大鼠，分离并冲洗其结肠或小肠，称取一段结肠（10 cm）或小肠（30 cm）的重量，并进行显微镜检查、NOS和髓过氧化物酶（MPO）活性以及PGE2生成的检测。结肠内或空肠内注射IA 48小时后导致广泛的宏观和微观损伤，同时伴有节段重量增加、MPO和NOS活性以及PGE2生成增加。在损伤诱导前48小时或损伤诱导时给予结肠SLP抗体，可显著减轻宏观和微观损伤、节段重量、MPO活性以及PGE2生成，但对NOS活性无影响。对照血清和针对SP-A的抗血清均无任何保护作用，IA给药后24小时注射抗结肠SLP抗血清也无保护作用。小肠SLP抗体对IA诱导的空肠炎无保护作用。静脉注射SLP抗体可改善IA诱导的结肠炎，但不能改善空肠炎，其机制尚待确定。这些数据为胃肠道SLP的生理作用提供了进一步的证据。
