上海交通大学学报(医学版)

• 论著(基础研究) • 上一篇    下一篇

乳凝集素对新生大鼠坏死性小肠结肠炎肠道损伤修复和TLR4表达的影响

雷一慧,沈海青,何雪梅,陈家慧,何振娟   

  1. 上海交通大学 医学院附属新华医院新生儿科上海市儿科医学研究所围产研究室, 上海 200092
  • 出版日期:2015-07-28 发布日期:2015-08-27
  • 通讯作者: 何振娟, 电子信箱: hezhenjuan@sjtu.edu.cn。
  • 作者简介:雷一慧(1987—), 女, 畲族, 硕士生; 电子信箱: yvonneleiyihui@126.com。
  • 基金资助:

    上海市科委基金(10411966100; 124119a5600)

Effects of lactadherin on repair of intestinal injury and expression of Toll-like receptor 4 of neonatal rats with necrotizing enterocolitis

LEI Yi-hui, SHEN Hai-qing, HE Xue-mei, CHEN Jia-hui, HE Zhen-juan   

  1. Department of Neonatology, Xinhua Hospital, Department of Perinatal Research Laboratory, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
  • Online:2015-07-28 Published:2015-08-27
  • Supported by:

    Foundation of Science and Technology Commission of Shanghai Municipality, 10411966100; 124119a5600

摘要:

目的  探讨乳凝集素(MFG-E8)对新生大鼠坏死性小肠结肠炎(NEC)肠道损伤修复和Toll样受体4 (TLR4)表达的影响。方法  采取缺氧冷应激联合配方奶侵袭性喂养建立NEC模型,将1日龄新生大鼠随机分为母乳组、NEC模型组和NEC联合重组人MFG-E8 (rhMFG-E8)组(N+M组),每组10只。N+M组在NEC模型组的基础上每日给予100 μg rhMFG-E8,喂养96 h后处死新生大鼠并观察肠道外观形态,取小肠回盲部组织进行组织病理学和透射电子显微镜检查。同时,采用real-time PCR和Western blotting检测小肠回盲部TLR4的表达。结果  rhMFG-E8可改善NEC肠道外观形态和显著降低NEC的发生率以及病理学评分(P<0.05);N+M组肠道TLR4的表达显著低于NEC模型组(P<0.05);N+M组肠道超微结构中未见典型凋亡细胞。结论  予以rhMFG-E8可明显降低TLR4的表达,降低肠上皮细胞凋亡,维持肠道屏障的完整性,减少新生大鼠模型NEC的发病率。

关键词: 坏死性小肠结肠炎, 乳凝集素, Toll样受体4

Abstract:

Objective  To investigate the effects of lactadherin (MFG-E8) on the repair of intestinal injury and expression of Toll-like receptor 4 (TLR4) of neonatal rats with necrotizing enterocolitis (NEC). Methods  NEC model was established by a combination of aggressive gavage with formula milk, hypoxia, and cold stress. A total of 30 one-day-old newborn rats were randomly divided into the breast milk group (n=10), NEC model group (N group, n=10), and NEC combined with recombinant human MFG-E8 (rhMFG-E8) group (N+M group, n=10). Based on the NEC model, rats of the N+M group were administrated with 100 μg of rhMFG-E8 daily. Rats were sacrificed after being fed for 96 h. Intestinal morphology was observed. The intestinal ileocecum tissue was collected and histopathological examination and transmission electron microscope (TEM) examination were conducted. TLR4 expression of intestinal ileocecum was detected by real-time PCR and Western blotting. Results  The rhMFG-E8 was capable of improving the intestinal appearance of rats with NEC and significantly decreasing the pathological score and incidence of NEC (P<0.05). The expression of TLR4 of the N+M group was significantly lower than that of the NEC model group (P<0.05). Typical apoptotic cells were not observed in intestinal ultra microstructure of the N+M group. Conclusion  Administration of rhMFG-E8 can significantly decrease the expression of TLR4 and apoptosis of intestinal epithelial cells, maintain the integrity of intestinal barrier, and reduce the incidence of NEC of neonatal rats.

Key words: necrotizing enterocolitis, lactadherin, Toll-like receptor 4