Recombinant human soluble thrombomodulin reduces the severity and incidence of necrotizing enterocolitis in a newborn rat model
Recombinant human soluble thrombomodulin reduces the severity and incidence of necrotizing enterocolitis in a newborn rat model
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DOI：
10.1007/s00595-019-01832-7
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发表时间：
2019-11-01
期刊：
影响因子：
2.5
通讯作者：
Okuyama, Hiroomi
中科院分区：
文献类型：
--
作者：
Li, Bo;Saka, Ryuta;Okuyama, Hiroomi
目的坏死性小肠结肠炎（NEC）是早产儿死亡的主要原因。已报道重组人可溶性血栓调节蛋白（rTM）具有抗炎作用以及抗血栓形成作用。本研究的目的是评估rTM在大鼠NEC模型中的作用。方法采用高渗配方肠内喂养、脂多糖灌胃和窒息应激诱导大鼠NEC。对照组由其母亲随意喂养。在治疗组中，rTM皮下给药两次（第一天和第二天各一次）。对存活超过96小时或出现痛苦体征的所有动物实施安乐死。收获回肠进行组织学评价并测量mRNA和蛋白质表达。结果治疗组NEC样肠损伤发生率（9/25，36%）明显低于NEC组（25/34，73.5%）。NEC组中TNF-α、IL-6和HMGB 1的组织水平显著升高，而治疗组中的组织水平降低至与对照组相似的值。结论rTM能降低NEC的严重程度和发病率。它可能是治疗NEC的一种替代选择。
Purpose Necrotizing enterocolitis (NEC) remains the leading cause of death in preterm infants. Recombinant human soluble thrombomodulin (rTM) has been reported to have anti-inflammatory effects as well as antithrombogenic effects. The aim of this study was to evaluate the effect of rTM in a rat NEC model. Methods NEC was induced by enteral feeding with hyperosmolar formula, gavage administration of lipopolysaccharide and asphyxia stress. Controls were fed by their mother ad libitum. In the treatment group, rTM was administered subcutaneously twice (once each on the first and second day). All animals surviving beyond 96 h or that developed signs of distress were euthanized. The ileum was harvested for a histological evaluation and the measurement of the mRNA and protein expression. Results The rate of NEC-like intestinal injury in the treatment group (9/25, 36%) was significantly lower than in the NEC group (25/34, 73.5%). Tissue levels of TNF-alpha, IL-6 and HMGB1 were significantly elevated in the NEC group, whereas those in the treatment group were decreased to similar values as in the control group. Conclusions Our experimental study showed that rTM is able to reduce the severity and incidence of NEC. It may be an alternative option for the treatment of NEC.