内皮祖细胞衰老的DNA损伤检测点ATM/ATR通路及黄精的干预作用机制

Endothelial progenitor cells(EPCs) play a critical role in the maintenance of arterial endothelium and the prevetion and control of atherosclerotic disease.However，EPCs senescence causes reduced number and dysfunction of cells， thus limites the the clinical application of EPCs.As EPCs senescence is closely related to Shenxu-Jingkui，and DNA damage is a core for cellular senescence，and Rhizoma Polygonati is used for anti-ageing and Bushen-Yijing in traditional Chinese medicine.We hypothesize that ATM/ATR DNA damage checkpoint pathway could be involved in EPCs senescence and Rhizoma Polygonati could be effective in prevention of EPCs senescence.To prove this，we will observe the effect of Rhizoma Polygonatiom on the functional activity of EPCs in natural ageing model of rat，and we will detect the ATM/ATR DNA damage checkpoint pathway in senescent EPCs cultured in vitro and the molecular mechanism of Rhizoma Polygonati on senescent EPCs.This research will provide both experimental and academic evidence for molecular mechanism of EPCs senescence and the anti-ageing effect of Chinese medicine for Bushen-Yijing.

内皮祖细胞（EPCs）具有维护动脉内皮完整性，防治动脉粥样硬化相关疾病的重要作用；然而EPCs的衰老却令其数量功能受损使EPCs的临床应用受到很大限制。EPCs的衰老与肾虚精亏关系密切，黄精是传统的补肾益精和延缓衰老的中药，我们拟从细胞衰老的核心环节—DNA损伤及DNA损伤检测点ATM/ATR通路来研究EPCs的衰老机制和黄精的干预作用。为此，本项目拟采用自然衰老大鼠模型，观察黄精对衰老大鼠EPCs功能的整体作用效果，并通过体外实验观察DNA损伤检测点ATM/ATR通路对EPCs衰老的影响及黄精的干预作用是否发生变化。本研究将为EPCs衰老机制的研究和补肾益精类中药延缓衰老的分子机制提供实验依据和理论依据。

内皮祖细胞（EPCs）具有维护动脉内皮完整性，防治动脉粥样硬化相关疾病的重要作用；然而EPCs的衰老却令其数量功能受损使EPCs的临床应用受到很大限制。EPCs的衰老与肾虚精亏关系密切，而黄精是传统的补肾益精和延缓衰老的中药，本项目从细胞衰老的核心环节—DNA损伤及DNA损伤检测点ATM/ATR通路研究了EPCs的衰老机制和黄精的干预作用，结果表明EPCs衰老的可能机制与细胞DNA损伤检测点ATM/ATR的活化有关，黄精可通过增强衰老大鼠体内抗氧化功能，提高细胞端粒酶活性，调控细胞DNA损伤检测点ATM/ATR通路来延缓EPCs的衰老进程，保护衰老EPCs的受损功能。本项目将为EPCs衰老机制的深入研究和补肾益精类中药延缓衰老的分子机制提供实验依据和理论依据。