Zhang Bing-Hong, Yu Hong-Gang, Sheng Zhi-Xiang, Luo He-Sheng, Yu Jie-Ping
Department of Gastroenterology, Renmin Hospital of Wuhan University, Jiefang Road 238, 430060, Wuhan, PR China.
Regul Pept. 2003 Nov 15;116(1-3):53-60. doi: 10.1016/s0167-0115(03)00177-0.
Trefoil peptides are a new class of regulatory peptides involved in mucosal protection and repair in the gastrointestinal tract. Among them, trefoil factor 3 (TFF3) (intestinal trefoil factor) is known to be cytoprotective in the gut. The aim of this study was to determine the effect of recombinant human trefoil factor 3 (rhTFF3) on hypoxia-induced necrotizing enterocolitis (NEC) in immature rats. In the present study, thirty-two 1-day-old Wistar rat pups were randomly divided into four groups. Group 1 served as nonhypoxic controls. Group 2 rats were subjected to hypoxia reoxygenation (H/O) and then were returned to their mothers. Groups 3 and 4 rats were subjected to H/O, were returned to their mothers, and were treated with rhTFF3 intraperitoneally (0.5 mg) and subcutaneously (0.2 mg), respectively, for the next 3 days. All animals were killed on day 4, and intestine specimens were obtained to determine the histological changes, tissue level of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), malondialdehyde (MDA), prostaglandin E2 (PGE2), tromboxane B2 (TXB2), and nitric oxide (NO). In addition, the effects of rhTFF3 on abundance of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) were also investigated. In neonatal NEC (group 2), necrosis of villi and crypts and, in some cases, transmural necrosis was observed under light microscopy. Tissue level of interleukin-8, tumor necrosis factor-alpha, malondialdehyde, prostaglandin E2, tromboxane B2, and nitric oxide were significantly higher than group 1. In addition, abundance of inducible nitric oxide synthase and cyclooxygenase 2 was markedly increased. In groups 3 and 4, only very slight intestinal injury was observed. The tissue level of interleukin-8, tumor necrosis factor-alpha, malondialdehyde, prostaglandin E2, tromboxane B2, and nitric oxide were significantly decreased in comparison to the group 2. Meanwhile, the abundance of inducible nitric oxide synthase and cyclooxygenase 2 was also marked decreased in comparison to group 2. The current study suggests a therapeutic role of TFF3 in an experimental model of NEC. Our findings may open a new insight into the treatment of NEC in newborns.
三叶肽是一类新的调节肽，参与胃肠道的黏膜保护和修复。其中，三叶因子3（TFF3）（肠三叶因子）已知在肠道中具有细胞保护作用。本研究的目的是确定重组人三叶因子3（rhTFF3）对未成熟大鼠缺氧诱导的坏死性小肠结肠炎（NEC）的影响。在本研究中，32只1日龄的Wistar大鼠幼崽被随机分为四组。第1组作为非缺氧对照组。第2组大鼠经历缺氧复氧（H/O），然后放回其母鼠身边。第3组和第4组大鼠经历H/O，放回其母鼠身边，并在接下来的3天分别腹腔注射（0.5毫克）和皮下注射（0.2毫克）rhTFF3。所有动物在第4天处死，获取肠道标本以确定组织学变化、白细胞介素-8（IL-8）、肿瘤坏死因子-α（TNF-α）、丙二醛（MDA）、前列腺素E2（PGE2）、血栓素B2（TXB2）和一氧化氮（NO）的组织水平。此外，还研究了rhTFF3对诱导型一氧化氮合酶（iNOS）和环氧化酶2（COX-2）丰度的影响。在新生儿NEC（第2组）中，光镜下观察到绒毛和隐窝坏死，在某些情况下还观察到透壁坏死。白细胞介素-8、肿瘤坏死因子-α、丙二醛、前列腺素E2、血栓素B2和一氧化氮的组织水平显著高于第1组。此外，诱导型一氧化氮合酶和环氧化酶2的丰度明显增加。在第3组和第4组中，仅观察到非常轻微的肠道损伤。与第2组相比，白细胞介素-8、肿瘤坏死因子-α、丙二醛、前列腺素E2、血栓素B2和一氧化氮的组织水平显著降低。同时，与第2组相比，诱导型一氧化氮合酶和环氧化酶2的丰度也显著降低。当前研究表明TFF3在NEC实验模型中具有治疗作用。我们的发现可能为新生儿NEC的治疗开辟新的思路。
