Cerebral inflammatory response after fetal asphyxia and hyperoxic resuscitation in newborn sheep
Cerebral inflammatory response after fetal asphyxia and hyperoxic resuscitation in newborn sheep
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DOI：
10.1203/pdr.0b013e31811ead6e
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发表时间：
2007-07-01
影响因子：
3.6
通讯作者：
Ley, David
中科院分区：
文献类型：
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作者：
Markus, Tina;Hansson, Stefan;Ley, David
胎儿窒息后出生时用纯氧复苏可能会导致促炎反应，从而加重脑损伤。Toll样受体(Toll-like Receptor，TLRs)可能在缺血再灌流时的高氧血症中起促炎作用。16只近足月胎羊(132~136d)在脐带阻断10min后分娩，分别用100%O2(n=8)或21%O2(n=8)进行30min的机械通气，然后进行常氧血症90min。8只绵羊胚胎立即分娩，吸氧120min(对照组)。IL-1β、TNF-α、IL-12p40、IL-18、IL-6、IL-10、干扰素-γ、TLR-2的mRNAs水平及分布。用实时定量聚合酶链式反应和原位杂交法检测出生后2 h脑组织中-3和-4的表达。复苏后100%O2组大鼠皮质/皮质下IL-1β、IL-12p40、TLR-2和TLR-4的表达明显高于21%O-2组(P均0.05)和对照组(P均0.05)。IL-1β的细胞表达增加局限于脑膜下皮质层和皮质下白质。胎儿窒息后出生时高氧复苏可诱导脑部促炎反应，上调TLR-2和-4的表达。这些可能是出生时暴露于高氧血症后导致组织损伤增加的早期事件。
Resuscitation with pure oxygen at birth after fetal asphyxia may aggravate brain damage by inducing pro-inflammation. The toll-like receptors (TLRs) may serve a pro-inflammatory role in hyperoxemia during ischemia-reperfusion. Sixteen near-term fetal sheep (132-136 d) were subjected to 10 min of cord occlusion, delivery and mechanical ventilation with 100% O-2 (n = 8), or 21% O-2 (n = 8) for 30 min followed by normoxemia for 90 min. Eight sheep fetuses were delivered immediately with inspired O-2 targeted at normoxemia for 120 min (controls). Levels and distributions of mRNAs for IL-1 beta, TNF-alpha, IL-12p40, IL-18, IL-6, IL-10, IFN-gamma, TLR-2. -3 and -4 in cerebral tissue at 2 h after birth were evaluated with real-time polymerase chain reaction (PCR) and in situ hybridization. Expressions of IL-1 beta, IL-12p40, TLR-2, and TLR-4 were increased in cortex/subcortex after resuscitation with 100% 02 compared with 21% O-2 (all p < 0.05) and to controls (all p < 0.05). Increased cellular expression of IL-1 beta was localized to sub-meningeal cortical layers and to sub-cortical white matter. Hyperoxic resuscitation at birth following fetal asphyxia induces a cerebral pro-inflammatory response with an up-regulation of TLR-2 and -4. These may be early events leading to increased tissue damage after exposure to hyperoxemia at birth.