目前认为自噬在动脉粥样硬化(AS)过程中发挥重要作用,AS是缺血性脑卒中的主要发病机制。研究显示lncRNA与miRNA能够调控自噬及AS进程,但lncRNA是否作用于miRNA调控自噬影响脑卒中发病尚不明确。我们前期研究发现大动脉粥样硬化型脑卒中(LAA)患者miR-155表达显著下降，lncRNA-MALAT1表达上调，PI3K/Akt/mTOR信号通路在血管内皮细胞自噬中具有重要调控作用，本研究拟进一步研究MALAT1、miR-155及通路分子表达与脑动脉AS的关系；采用ox-LDL诱导HUVEC,报告基因实验验证MALAT1/miR-155调控该通路的靶点,明确MALAT1/miR-155靶向调控PI3K/Akt/mTOR信号通路在血管内皮细胞自噬的作用机制；动物实验证实其对颈动脉AS的干预作用,为阐明脑动脉AS的分子发病机制夯实理论基础,为LAA的防治寻找新的靶点。

It is widely believed that autophagy plays crucial roles in the pathological process of atherosclerosis, and atherosclerosis is the main pathogenesis of ischemic stroke. .Long non-coding RNAs (lncRNAs) and microRNA（miRNAs ）are both non-coding RNAs. It has been reported that lncRNAs could regulate the expression of miRNAs acting as competing endogenous RNAs (ceRNAs). Literature and our previous studies have shown that long non-coding RNAs (lncRNAs) and microRNA （miRNAs）could regulate autophagy and the processes of atherosclerosis, and are closely related to stroke of large artery atherosclerosis subtype（LAA）, which suggests that lncRNAs might act on the roles of miRNAs in the regulation of autophagy, and have an effect on the occurrence of LAA stroke. .Our previous experiments showed that miR-155 expression in LAA patients was significantly decreased, while lncRNA-MALAT1 expression was significantly up-regulated. What’s more, PI3K/Akt/mTOR signaling pathway plays an important role in the regulation of autophagy in vascular endothelial cells. To explore the relationship between MALAT1, miR-155 and PI3K/Akt/mTOR signaling pathway, together with their roles in LAA stroke, we are going to detect the expression of PI3K、p-Akt、Akt、Rheb、p-p70s6k、p70s6k mRNA and protein in peripheral blood mononuclear cells from the patients with LAA using methods of real-time quantitative reverse transcription polymerase chain reaction（qRT-PCR）and West-blot respectively. Furthermore，we explore the regulation targets of MALAT1 on miR-155，and miR-155 on PI3K/Akt/mTOR signal pathway in human umbilical vein endothelial cells induced by oxidized Low density lipoprotein（ox-LDL）, and test their roles invivo. This would be helpful to elucidate the regulation mechanism of miRNAs on TLR4/NF-κB/CXCL16 signal transduction pathway in atherosclerosis, which may be helpful to find new targets for the prevention and therapy of LAA.

目前认为自噬在动脉粥样硬化(AS)过程中发挥重要作用,AS是缺血性脑卒中的主要发病机制。研究显示lncRNA与miRNA能够调控自噬及AS进程,但lncRNA是否作用于miRNA调控自噬影响脑卒中发病尚不明确。我们前期研究发现大动脉粥样硬化型脑卒中(LAA)患者miR-155表达显著下降，lncRNA-MALAT1表达上调，PI3K/Akt/mTOR信号通路在血管内皮细胞自噬中具有重要调控作用，本研究拟进一步研究MALAT1、miR-155及通路分子表达与脑动脉AS的关系；采用ox-LDL诱导HUVEC,报告基因实验验证MALAT1/miR-155调控该通路的靶点,明确MALAT1/miR-155靶向调控PI3K/Akt/mTOR信号通路在血管内皮细胞自噬的作用机制；动物实验证实其对颈动脉AS的干预作用,为阐明脑动脉AS的分子发病机制夯实理论基础,为LAA的防治寻找新的靶点。