miRNA-151调节TLR9/TRAF6信号通路在肠I/R损伤后细菌移位的作用及机制

肠缺血再灌注（I/R）后肠内细菌移位是导致MODS的重要原因之一，其机制尚未明了。已证实TLR9/TRAF6信号通路在调节免疫炎症反应中发挥关键作用，申请者预实验发现TLR9抑制剂能抑制该通路的激活并显著减少肠I/R后细菌移位，提示TLR9/TRAF6通路与肠I/R后细菌移位有关。miRNA是新型的负性基因调控剂，其是否介导I/R后肠内细菌移位尚无报道。申请者新近筛选出miR-151在肠I/R后的肠粘膜组织中表达下调（Cell Death Dis, 2017），进一步采用生物信息学软件预测，发现TLR9是miR-151负性调控的一个靶基因。据此，申请者推测：肠I/R后肠粘膜miR-151表达下调，对TLR9负性调节作用减弱，从而激活TLR9/TRAF6信号导致炎症反应的发生，最终导致肠内细菌移位。本项目将通过一系列的体内外实验来验证该假说，为寻找防治肠I/R损伤可供干预的靶点提供理论基础。

Bacterial translocation after intestinal ischemia/reperfusion (I/R) injury is the major cause of Multiple Organ Dysfunction Syndrom, but its pathogenes remains unclear. In recent years, researches have confirmed that TLR9/TRAF6 signaling pathways is playing a key role in regulating the immune inflammatory response. We previously found that Sup ODN(TLR9 selective inhibitor) could reduce bacterial traslocation following intestinal I/R injury. miRNAs are novel class of endogenous, small non-coding single-stranded RNAs, which could downregulate gene expression by degrading target mRNAs and/or inhibiting protein synthesis. However, the contributions of miRNAs to mediate bacterial translocation after intestinal I/R injury remain to be elucidated. We recently found that intestinal I /R injury could decrease the expression of miR-151 in intestinal mucous（Cell Death Dis, 2017）, and the we found that TLR9 is one of the negative regulated target gene of miR-151 by using of bioinformatics software. Based on the above findings, we hypothesize that intestinal I/R could down-regulating the expression of miR-151 which could activate the TLR9/TRAF6 signaling pathway and lead to bacterial translocation. Therefore, the present study aims to verify this hypothesis via a series of in vivo and in vitro experiments. This study will provide scientific basis for seeking for therapeutic targets which can be intervened in prevention of intestinal I/R injury.