Chemerin通过调节p38MAPK通路参与动脉粥样硬化分子机制研究

At present, some scholars considered that inflammation is an important factor in the occurrence and development of atherosclerosis (AS). Chemerin was identified as a new adipokine in 2007. Studies have shown that there is a close relationship between chemerin and immune response to vascular inflammation. Recent some studies have found chemerin is related with the formation of atherosclerosis. It significantly increases the cholesterol uptake of human macrophage and is beneficial to the formation of foam cells. Damage and repair reaction mediated by EPCs is the initiation factor and an important part of AS. The number of EPCs in patients with coronary heart disease decreased in the study, whose mechanism is not clear. It may be related to interfering the signal pathway of regulating the differentiation of EPCs, which causes EPCs apoptosis depletion. In human endothelial cells, Chemerin activates and regulate MAPK and AKT pathways of angiogenesis in human endothelial cells, and induces angiogenesis. However, there is no literature about whether Chemerin affects proliferation and differentiation of cells by regulating the pathway of p38MAPK in the EPCs. This study investigated the molecular mechanisms of Chemerin through in vivo and in vitro in patients with AS, which provides new targets for AS study.

目前学者认为炎症反应是动脉粥样硬化(AS)发生和发展的重要因素。Chemerin于2007年被确认为新脂肪因子，有文献表明Chemerin与免疫应答血管炎症反映有密切关系。新近有研究发现，Chemerin能够明显增加人巨噬细胞对胆固醇的摄取并且有利于泡沫细胞的形成，认为Chemerin与动脉粥样硬化斑块的形成有关。内皮祖细胞(EPCs)介导的损伤和修复反应是AS的始动因素和重要环节。冠心病患者EPCs数量较正常人减少，其原因目前尚不清楚，可能与干扰调节EPCs分化动员的信号通路、促使骨髓EPCs的凋亡有关。在人内皮细胞中，Chemerin能够激活调节血管形成的MAPK和AKT通路，诱导新生血管形成，而在EPCs中Chemerin是否通过调控p38MAPK通路影响细胞的增殖及分化能力尚未见文献报道。本研究通过体内和体外探讨Chemerin参与AS的分子作用机制，为AS的研究提供新的靶点。

Chemerin可通过p38MAPK通路影响血管内皮祖细胞的功能从而参与动脉粥样硬化的发生发展，本课题通过WB,MTT,流式细胞分析等方法，对Chemerin参与调节内皮祖细胞功能的分子机制进行了初步的研究。成功分离、培养、鉴定内皮祖细胞之后以不同浓度的重组人Chemerin蛋白进行刺激，取得阳性结果后选取最适浓度对内皮祖细胞进行不同时间的刺激，结果表明Chemerin可以剂量-时间依赖性的方式增强内皮祖细胞的黏附及迁移能力；流式细胞分析结果显示，Chemerin可以剂量-时间依赖性的方式影响内皮祖细胞的凋亡，WB结果显示，Chemerin可以以剂量依赖性方式减少凋亡，减轻炎症；MTT结果显示Chemerin可以剂量-时间依赖性的方式影响内皮祖细胞的增殖能力，在拮抗p38MAPK通路之后，以上Chemerin对内皮祖细胞的作用均减弱。综合上述工作成果为后续探讨Chemerin如何参与动脉粥样硬化病理生理过程提供了坚实的基础。项目资助已发表文章4篇，授权专利1项，申请专利1项，待发表论文2篇。培养科研型硕士生1名，专业型硕士1名，均在读。