Vitamin D ameliorates neonatal necrotizing enterocolitis via suppressing TLR4 in a murine model
Vitamin D ameliorates neonatal necrotizing enterocolitis via suppressing TLR4 in a murine model
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维生素 D 通过抑制小鼠模型中的 TLR4 改善新生儿坏死性小肠结肠炎
DOI：
10.1038/pr.2017.329
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发表时间：
2018-05-01
影响因子：
3.6
通讯作者：
Xue, Xindong
中科院分区：
文献类型：
--
作者：
Shi, Yongyan;Liu, Tianjing;Xue, Xindong
研究背景Toll样受体4（TLR 4）在坏死性小肠结肠炎（NEC）中起重要作用。作为TLR 4的既定调节剂，维生素D已被证明具有神经保护作用。本研究旨在探讨维生素D/维生素D受体（vitamin D/vitamin D receptor，VDR）通路是否通过调节TLR 4而改善NEC。方法检测15例NEC早产儿、12例无并发症早产儿和20例健康足月儿血清25-羟维生素D（25（OH）D）水平，并进行比较。将新生Wistar大鼠分组，通过配方饲料和冷/窒息应激诱导NEC。维生素D和车辆进行了管理，比较显微结构，凋亡蛋白表达，肠屏障功能，炎症反应，和TLR 4 expression. ResultsNEC早产儿有显着降低25（OH）D水平比那些没有NEC和健康受试者。VDR表达被抑制，而TLR 4表达在NEC肠中升高。维生素D可提高存活率，减轻结构损伤，保护肠屏障功能。结论NEC患儿维生素D水平较低。维生素D/VDR通路可能通过抑制TLR 4的表达而对NEC肠损伤起到保护作用。
BackgroundThe toll-like receptor 4 (TLR4) has been reported to play an important role in necrotizing enterocolitis (NEC). As an established regulator of TLR4, vitamin D has been demonstrated to be intestinal-protective. This study aims at finding out whether the vitamin D/vitamin D receptor (VDR) pathway ameliorates NEC by regulating TLR4.MethodsSerum 25-hydrovitamin D (25 (OH) D) was tested and compared in 15 preterm infants with NEC, 12 preterm infants without known complications and 20 healthy term infants. Neonatal Wistar rats were grouped and NEC was induced through formula feeding and cold/asphyxia stress. Vitamin D and the vehicle were administered to compare the microscopic structure, apoptotic protein expression, intestinal barrier function, inflammatory response, and TLR4 expression.ResultsPreterm infants with NEC had significantly lower 25 (OH) D levels than those without NEC and healthy subjects. VDR expression was suppressed, whereas TLR4 expression was elevated in the NEC intestine. Vitamin D may increase the survival rate, alleviate structure damage, and preserve intestinal barrier function. These were achieved partly through restoration of VDR and suppression of TLR4.ConclusionNEC infants have lower levels of vitamin D. The vitamin D/VDR pathway protects against intestinal injury of NEC partly through suppressing the expression of TLR4.