细胞老化伴随吞噬能力的下降。血管内皮细胞有较强的吞噬功能，但其老化后吞噬能力改变情况、及其意义和机制尚不清楚。近期我们发现，老化的内皮吞噬血小板能力减弱且Girdin蛋白表达降低，抑制Girdin表达可阻断内皮吞噬血小板。吞噬血小板后内皮细胞增殖及抗凋亡能力增强。据此我们提出Girdin蛋白介导内皮吞噬血小板，该过程参与内皮细胞老化的假设。我们将在培养的血管内皮细胞、小鼠及人体组织标本中利用电镜、免疫荧光、流式细胞分析等技术，定性及定量观察内皮对血小板的吞噬；通过向小鼠体内注射荧光标记的血小板，确定年青、年老内皮吞噬血小板能力的差别；进一步分析抑制吞噬血小板削弱内皮增殖、迁移及加速凋亡、衰老的分子机制，包括探索AKT/ERK信号通路的活化情况；同时阐明内皮老化与Girdin表达下降间的关系以及Girdin调控内皮吞噬血小板的分子机制。本项目将为探索血管内皮细胞老化的机制提供新认识。

Phagocytosis decreased with cellular aging. Although the strong phagocytotic ability is well known to vascular endothelial cells, it remains unclear about the capacity of endothelial cells engulfing platelets, the significance and mechanism of this process in aged endothelium. Our recent study on aged endothelium demonstrated that both the ability of endothelial cells uptaking platelets and the expression level of endothelial cells decreased when compared with the young endothelium. Furthermore, when Girdin was suppressed, the number of platelets that were uptaken by endothelial cells was inhibited too. We also found that those endothelial cells that uptook platelets were provided with more powerful ability of proliferation and anti-apoptosis. Based on all the above, we speculate that Girdin involves in the procedure that endothelial cells uptake platelets and this phagocytosis takes part in the aging process of endothelial cells. In this study, the cultured endothelial cells, tissues from mouse and human will be used for immunofluorescent, flow cytometric and transmission electron microscopic analysis in order to confirm the phagocytosis qualitatively and quantitatively. Platelets labeled with PKH-26 will be injected into the mice to evaluate the difference of the phagocytosis between the young and the aged endothelium. We will further explore the molecular mechanisms of inhibition of platelets phagocytosis to attenuate the ability of endothelium to proliferate, migrate, and promote apoptosis/aging with the activation of AKT/ERK signaling pathway included. In addition, we will also clarify the relationship between aged endothelium and decrease of Girdin and the mechanism of Girdin mediated phagocytosis of platelets by endothelium. The results of this study will provide a new understanding for the mechanism of the aging of vascular endothelial cells.