NAD+/CD38/cADPR信号通路介导脓毒症脑病的分子机制研究

项目名称： NAD+/CD38/cADPR信号通路介导脓毒症脑病的分子机制研究

项目编号： No.81501649

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 彭倩宜

作者单位： 中南大学

项目金额： 18万元

中文摘要： 脓毒症脑病（SAE）是脓毒症的常见并发症，发病率、死亡率高，缺乏有效治疗手段，是近年来研究的热点。我们前期研究通过全基因组表达谱芯片比较分析，发现CD38基因在SAE大鼠与正常大鼠脑组织中存在显著性差异表达，进一步预实验显示SAE大鼠脑组织内NAD+、CD38和cADPR表达均显著增加且具有时间规律性，给予cADPR抑制剂处理后SAE脑损伤明显减轻，强烈提示NAD+/CD38/cADPR信号通路参与介导SAE的发生发展。本项目将从体外和体内两个层面，通过基因重组技术探究NAD+/CD38/cADPR信号通路的激活和抑制对SAE发生发展的影响；探索脂筏介导该通路活化的重要作用；研究该通路介导SAE脑损伤的下游分子机制。最终诠释NAD+/CD38/cADPR信号通路介导SAE的重要作用及其分子机制，研究结果将为SAE的治疗提供新思路和理论依据。

中文关键词： 脓毒症脑病；CD38；环腺苷二磷酸核糖；钙离子；脂筏

英文摘要： Sepsis associated encephalopathy (SAE) is a common complication of sepsis, with a high incidence and mortality rate, and still without effective treatment. Thus, it becomes a hot research topic recent years. In previous study, we did gene expression profile analysis and identified significantly differential expression of CD38 gene between the brain tissues of SAE and normal rats. Further experiments showed that NAD+, CD38 and cADPR expression significantly up-regulated in the brain tissues of SAE rats in a time-dependent pattern, and cADPR inhibitor treatment significantly alleviated the cerebral injury, which strongly indicated that the NAD+/CD38/cADPR signaling pathway took part in the pathogenesis of SAE. This project plan to use gene recombination technology to activate or inhibit the NAD+/CD38/cADPR signaling pathway and investigate its role in the pathogenesis of SAE; explore the important role of lipid rafts in the activation of this pathway; and study its downstream mechanisms that mediate the cerebral injury. The objective of this project is to clarify the role of NAD+/CD38/cADPR signaling pathway in SAE, therefore provide a new potential target for its treatment.

英文关键词： sepsis associated encephalopathy;CD38;cyclic adenosine diphosphoribose;calcium ion;lipid raft