下丘脑室旁核TLR4介导的AVP能神经元敏感化在急性胃黏膜损伤中的双向调节作用及其机制

项目名称： 下丘脑室旁核TLR4介导的AVP能神经元敏感化在急性胃黏膜损伤中的双向调节作用及其机制

项目编号： No.U1504813

项目类型： 联合基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 高林

作者单位： 郑州大学

项目金额： 27万元

中文摘要： 下丘脑室旁核AVP能神经元在胃缺血-再灌注损伤调控方面发挥重要作用。我们的前期工作证实，内脏大神经的活动强弱与胃缺血-再灌注损伤程度密切相关；而在下丘脑区域，给予TLR4或NF-κB阻断剂可使内脏大神经紧张度降低，减轻胃缺血-再灌注损伤。这提示我们TLR4和NF-κB与AVP能神经元敏感化以及其和内脏大神经之间的联系值得关注。而TLR4在下丘脑室旁核内主要表达于小胶质细胞。因此，本项目拟以室旁核小胶质细胞TLR4介导的MyD88依赖性和MyD88非依赖性信号通路为切入点，以NF-κB为研究重心，应用基因敲除、核团微量注射、RT-PCR、免疫印迹、共聚焦、电生理、微透析、免疫荧光等方法，以胃黏膜损伤指数、胃黏膜血流量和内脏大神经活动变化为观察终点和分析手段，探讨小胶质细胞TLR4介导NF-κB激活对炎症因子、AVP能神经元、肾素-血管紧张素系统等的影响，为胃黏膜缺血-再灌注损伤提供新的视角。

中文关键词： 休克；早期诊断；缺血再灌注损伤；核因子-κB；RNA干扰

英文摘要： AVP Neurons of the hypothalamus paraventricular nucleus play an important role in the gastric ischemia-reperfusion injury. Our preliminary experimental results confirmed that the strength of the Greater Splanchnic Nerve (GSN) activity is closely related to the degree of gastric ischemia-reperfusion injury, and in the region of the hypothalamus, giving the TLR4 or the NF-κB blockers can reduce GSN tensity, decrease the gastric ischemia-reperfusion injury. This reminder us that AVP neurons sensitization and the connection between its and the GSN are worth to study . Data have showed that microglia activation is the main source of inflammatory mediators in central nervous system and the key of neurons sensitization. Therefore, this project put the microglia TLR4 mediating dependency MyD88 and independence MyD88 signaling pathway as the breakthrough point in paraventricular nucleus, and the NF-κB as a center of research and application of gene knockout, nucleus accumbens trace injection, RT-PCR, Western Blot, Confocal, Electrophysiology, Immunofluorescence, such as experimental method, in gastric mucosa damage index, the gastric mucosal blood flow and GSN activity changes to observe the finish and the analysis method, explore the TLR4 mediating the NF-κB activated microglial cells can neurons on the AVP, renin - angiotensin system, the influence of inflammatory cytokines and reactive oxygen species, provide a new perspective for acute gastric mucosal ischemia-reperfusion injury.

英文关键词： Shock;Early diagnosis ;Ischemia-reperfusion injury;Nuclear factor kappa B;RNA interference