动脉粥样硬化（AS）是一种受脂质刺激的慢性炎症性疾病，是心血管疾病引起的重要原因。间充质干细胞已被用于治疗动脉粥样硬化病变。脂肪源干细胞（ADSCs）已显示调节巨噬细胞激活状态和具有抗炎能力。然而，同种异体ADSCs在治疗动脉粥样硬化方面的效果尚未被研究。本研究探讨了异基因兔ADSCs静脉移植在高脂饮食兔模型中的早期治疗效果和初步机制分析。进一步在体外分析了兔ADSCs对巨噬细胞的极化机制。与模型组相比，血脂水平降低，斑块面积、氧化低密度脂蛋白（ox-LDL）摄取、清道夫受体A1和簇半脂质类受体（CD36）水平显著降低，并且炎症M1巨噬细胞的积累、凋亡、白细胞介素（IL）-6和肿瘤坏死因子（TNF）-α的表达减少。内皮细胞（CD31）、M2巨噬细胞、IL-10和转化生长因子（TGF）-β水平增加。体外实验中发现，ADSCs可以通过其分泌的外泌体促使M1巨噬细胞表型切换为M2巨噬细胞，其主要机制包括增加精氨酸酶1的表达和IL-10的分泌，降低诱导型一氧化氮合酶（iNOS）的表达和TNF-α的分泌，并激活STAT6通路。因此，异基因兔ADSC移植可以穿越至主动脉动脉粥样硬化斑块，通过抑制ox-LDL摄取、炎症反应和内皮损伤，在动脉粥样硬化早期阶段显示出降低血脂和缓解动脉粥样硬化斑块的良好效果。

Atherosclerosis (AS) is a chronic inflammatory disease of arteries fueled by lipids. It is a major cause of cardiovascular morbidity and mortality. Mesenchymal stem cells have been used for the treatment of atherosclerotic lesions. Adipose-derived stem cells (ADSCs) have been shown to regulate the activation state of macrophages and exhibit anti-inflammatory capabilities. However, the effect of allogeneic ADSCs in the treatment of AS have not been investigated. In this study, the early treatment effect and preliminary mechanism analysis of allogeneic rabbit ADSCs intravenous transplantation were investigated in a high-fat diet rabbit model. The polarization mechanism of rabbit ADSCs on the macrophage was further analyzed in vitro. Compared with the model group, blood lipid levels declined, the plaque area, oxidized low-density lipoprotein (ox-LDL) uptake, scavenger receptor A1 and cluster of differentiation (CD) 36 levels were all significantly reduced, and the accumulation of inflammatory M1 macrophages, apoptosis, interleukin (IL)-6 and tumor necrosis factor (TNF)-α expression were decreased. The endothelial cells (CD31), M2 macrophages, IL-10 and the transforming growth factor (TGF)-β levels increased. In vitro, ADSCs can promote the M1 macrophage phenotypic switch toward the M2 macrophage through their secreted exosomes, and the main mechanism includes increasing arginase 1 expression and IL-10 secretion, declining inducible nitric oxide synthase (iNOS) expression and TNF-α secretion, and activating the STAT6 pathway. Therefore, allogeneic rabbit ADSC transplantation can transmigrate to the aortic atherosclerotic plaques and show a good effect in lowering blood lipids and alleviating atherosclerotic plaque in the early stage of AS by inhibiting ox-LDL uptake, inflammatory response, and endothelial damage.