Postinjury vagal nerve stimulation protects against intestinal epithelial barrier breakdown.
Postinjury vagal nerve stimulation protects against intestinal epithelial barrier breakdown.
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DOI：
10.1097/ta.0b013e318216f754
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发表时间：
2011-05
期刊：
影响因子：
--
通讯作者：
Coimbra R
中科院分区：
文献类型：
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作者：
Krzyzaniak M;Peterson C;Loomis W;Hageny AM;Wolf P;Reys L;Putnam J;Eliceiri B;Baird A;Bansal V;Coimbra R
迷走神经刺激（VNS）具有明显的抗炎作用。我们之前的研究表明，损伤前VNS可阻止肠屏障的破坏，并保留上皮紧密连接蛋白的表达。然而，预处理模型对创伤患者的护理几乎没有临床意义。因此，我们假设在损伤后进行VNS对维持肠上皮屏障完整性也具有类似的保护作用。在损伤后15、30、60、90、120和150分钟，对雄性balb/c小鼠进行30%体表面积的全层蒸汽烧伤，然后进行右侧颈椎VNS。通过对4 kDa异硫氰酸-葡聚糖荧光素的通透性、组织学评估、肠道肿瘤坏死因子-α (TNF-α)酶联免疫吸附试验以及免疫印迹和免疫荧光法检测紧密连接蛋白（肌球蛋白轻链激酶、occludin和ZO-1）的表达来量化肠道屏障功能障碍。组织学检查显示，如果在烧伤后90分钟内进行颈椎VNS，肠绒毛外观与假手术相似。损伤后VNS≤90分钟时，肠对异硫氰酸-葡聚糖荧光素的通透性降低。烧伤引起肠道TNF-α水平显著升高。在损伤后90分钟内进行VNS治疗的动物TNF-α水平与假手术相似。如果在烧伤后90分钟内进行VNS，则紧密连接蛋白的表达维持在接近假值的水平，而烧伤后表达明显改变。损伤后VNS可在热损伤90分钟内防止肠上皮破坏。这可能代表了一个治疗窗口和临床相关的策略，以防止创伤后远处器官损伤的全身炎症反应。
Vagal nerve stimulation (VNS) can have a marked anti-inflammatory effect. We have previously shown that preinjury VNS prevented intestinal barrier breakdown and preserved epithelial tight junction protein expression. However, a pretreatment model has little clinical relevance for the care of the trauma patient. Therefore, we postulated that VNS conducted postinjury would also have a similar protective effect on maintaining gut epithelial barrier integrity. Male balb/c mice were subjected to a 30% total body surface area, full-thickness steam burn followed by right cervical VNS at 15, 30, 60, 90, 120, and 150 minutes postinjury. Intestinal barrier dysfunction was quantified by permeability to 4 kDa fluorescein isothiocyanate-Dextran, histologic evaluation, gut tumor necrosis factor-alpha (TNF-α) enzyme-linked immunosorbent assay, and expression of tight junction proteins (myosin light chain kinase, occludin, and ZO-1) using immunoblot and immunoflourescence. Histologic examination documented intestinal villi appearance similar to sham if cervical VNS was performed within 90 minutes of burn insult. VNS done after injury decreased intestinal permeability to fluorescein isothiocyanate-Dextran when VNS was ≤90 minutes after injury. Burn injury caused a marked increase in intestinal TNF-α levels. VNS-treated animals had TNF-α levels similar to sham when VNS was performed within 90 minutes of injury. Tight junction protein expression was maintained at near sham values if VNS was performed within 90 minutes of burn, whereas expression was significantly altered in burn. Postinjury VNS prevents gut epithelial breakdown when performed within 90 minutes of thermal injury. This could represent a therapeutic window and clinically relevant strategy to prevent systemic inflammatory response distant organ injury after trauma.