Vagal nerve stimulation protects against burn-induced intestinal injury through activation of enteric glia cells
Vagal nerve stimulation protects against burn-induced intestinal injury through activation of enteric glia cells
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迷走神经刺激通过激活肠神经胶质细胞防止烧伤诱导的肠道损伤
DOI：
10.1152/ajpgi.00156.2010
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发表时间：
2010-12-01
影响因子：
4.5
通讯作者：
Coimbra, Raul
中科院分区：
文献类型：
--
作者：
Costantini, Todd W.;Bansal, Vishal;Coimbra, Raul
肠神经系统可能通过肠胶质细胞的激活，在调节胃肠道屏障对疾病的反应中起重要作用。体外研究表明，肠胶质细胞激活通过改变紧密连接蛋白的表达来改善肠上皮屏障功能。我们假设严重的损伤会增加胶质纤维酸性蛋白（GFAP）的表达，GFAP是肠胶质细胞激活的标志。我们还试图通过系统性损伤和局部肠粘膜受累模型来确定迷走神经刺激对肠胶质细胞激活和肠屏障功能的影响。以体表面积为30%的蒸汽烧伤小鼠为重度损伤模型。通过迷走神经刺激来评估副交感神经信号在肠胶质细胞激活中的作用。在体内测量肠通透性以评估屏障功能。取肠观察组织学变化；通过定量PCR、共聚焦显微镜和GFAP荧光素酶转基因小鼠检测GFAP的表达。刺激迷走神经可预防损伤性肠屏障损伤。肠道GFAP表达在烧伤后的早期时间点增加，并在损伤后24小时恢复到基线水平。损伤前的迷走神经刺激比单独烧伤更能增加GFAP的表达。在GFAP-荧光素酶转基因动物中，在严重烧伤或迷走神经刺激后，胃肠道生物发光成像证实了肠道GFAP的表达增加。烧伤后注射s -亚硝基谷胱甘肽（一种由激活的肠胶质细胞释放的信号分子）具有类似于迷走神经刺激的保护作用。严重烧伤后肠道GFAP表达增加。刺激迷走神经增加肠胶质细胞的激活，这与改善肠屏障功能有关。迷走神经可能介导胃肠道损伤后从中枢神经系统到肠神经系统的信号传递。
The enteric nervous system may have an important role in modulating gastrointestinal barrier response to disease through activation of enteric glia cells. In vitro studies have shown that enteric glia activation improves intestinal epithelial barrier function by altering the expression of tight junction proteins. We hypothesized that severe injury would increase expression of glial fibrillary acidic protein (GFAP), a marker of enteric glial activation. We also sought to define the effects of vagal nerve stimulation on enteric glia activation and intestinal barrier function using a model of systemic injury and local gut mucosal involvement. Mice with 30% total body surface area steam burn were used as model of severe injury. Vagal nerve stimulation was performed to assess the role of parasympathetic signaling on enteric glia activation. In vivo intestinal permeability was measured to assess barrier function. Intestine was collected to investigate changes in histology; GFAP expression was assessed by quantitative PCR, by confocal microscopy, and in GFAP-luciferase transgenic mice. Stimulation of the vagus nerve prevented injury-induced intestinal barrier injury. Intestinal GFAP expression increased at early time points following burn and returned to baseline by 24 h after injury. Vagal nerve stimulation prior to injury increased GFAP expression to a greater degree than burn alone. Gastrointestinal bioluminescence was imaged in GFAP-luciferase transgenic animals following either severe burn or vagal stimulation and confirmed the increased expression of intestinal GFAP. Injection of S-nitrosoglutathione, a signaling molecule released by activated enteric glia cells, following burn exerts protective effects similar to vagal nerve stimulation. Intestinal expression of GFAP increases following severe burn injury. Stimulation of the vagus nerve increases enteric glia activation, which is associated with improved intestinal barrier function. The vagus nerve may mediate the signaling that occurs from the central nervous system to the enteric nervous system following gastrointestinal injury.