氧化应激(OS)诱导的内皮损伤和炎症反应是动脉粥样硬化(AS)的两个关键发病机制。淫羊藿苷(ICAR)可以促进内皮祖细胞(EPC)归巢和分化，有效抑制AS形成，但具体机制还不清楚。我们的前期工作发现ICAR可能通过调控mTOR和p38 MAPK信号通路，促进EPC成血管分化，拮抗OS和内质网应激(ERS)诱导的细胞损伤和炎症反应，并能调控细胞凋亡与自噬。据此假设ICAR通过调控mTOR和p38 MAPK信号通路及其下游关键转录因子4EBP1和ATF2，抑制OS和ERS介导的细胞凋亡和自噬性死亡，修复AS内皮损伤。通过检测应激条件下ICAR对EPC在体内的归巢和分化、体外的凋亡和自噬的影响，并阻断相关信号位点后观察细胞损伤情况及相关蛋白差异表达，进一步阐明mTOR和p38 MAPK信号通路在ICAR促进EPC修复AS内皮损伤中的调控机制，为ICAR治疗动脉粥样硬化性心脏病提供新的理论依据。

Reduced tissue levels of endothelial progenitor cells (EPCs) and functional impairment of endothelium are frequently observed in patients with atherosclerosis and other cardiovascular disease. The vascular endothelium is specifically sensitive to oxidative stress, and this is one of the mechanisms that causes widespread endothelial dysfunction in most cardiovascular diseases and disorders. Hence attention has increasingly been paid to enhance mobilization and differentiation of EPCs for therapeutic purposes. Icariin, a natural bioactive component known from Traditional Chinese Medicine, can induce angiogenic differentiation and inhibit oxidative stress-induced cell dysfunction in bone marrow derived EPCs (BM-EPCs), but the underlying mechanisms are not well understood. We observed that treatment of BM-EPCs with Icariin significantly promoted cell migration and capillary tube formation, substantially abrogated hydrogen peroxide (H2O2)-induced apoptotic and autophagic programmed cell death that was linked to the reduced intracellular reactive oxygen species (ROS) levels and restored mitochondrial membrane potential (MMP). These anti-apoptotic and anti-autophagic effects of Icariin are possibly mediated by restoring the loss of Akt/mTOR/4EBP1 phosphorylation as well as attenuation of p38 MAPK/ATF2 protein levels after H2O2 treatment. We accordingly suppose that Akt/mTOR/4EBP1 and p38 MAPK/ATF2 signaling pathways may play important roles in attenuation of oxidative stress and endoplasmic reticulum stress-induced cell apoptosis and autophagy, therefore contributing to the repairment of endothelial injury. We plan to reveal the underlying mechanisms of angiogenic and protective effect of Icariin via detecting the effect of Icariin on homing and angiogenic differentiation of EPCs in vitro and in vivo, on cell apoptosis and autophagy under the oxidative stress and endoplasmic reticulum stress, and determining the corresponding expression of proteins, thus making Icariin as novel proangiogenic and cytoprotective therapeutic agent with potential applications in the fields of coronary atherosclerotic heart disease.