目的 探讨黄精通过调节心脏DNA损伤应答毛细血管共济失调突变基因（ATM）、ATM与Rad3相关蛋白激酶（ATR）通路对自然衰老大鼠心脏的保护作用。方法 取16只SD大鼠（2月龄）为青年组，另将64只SD大鼠（18月龄）随机分为衰老组、黄精低、中、高剂量组，每组16只；青年组和衰老组灌胃等量蒸馏水，黄精低、中、高剂量组灌胃黄精水煎液1、2、4 g/kg，每天 1 次，连续灌胃12周。第4、12周时，每组取8只大鼠麻醉处死，分离心脏并计算心重指数，观察心脏组织病理变化，检测心脏组织总抗氧化能力（T-AOC）、谷胱甘肽过氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）、丙二醛（MDA）含量及ATM、ATR通路相关蛋白的表达。结果 随周龄增加，衰老组大鼠在第12周时其心肌细胞明显肿大、胞间隙增宽、心肌纤维排列紊乱并断裂，心肌纤维化面积增多，心脏组织GSH-Px含量降低、MDA含量升高、细胞周期检测点激酶1（Chk1）蛋白表达上调（P < 0.05）；同周次内比较，衰老组大鼠较青年组心重指数降低，心脏组织T-AOC、SOD、GSH-Px含量降低，MDA含量升高；ATM、ATR通路相关蛋白表达均显著上调（P < 0.05）；经黄精干预后，衰老大鼠心重指数有所升高，心肌细胞结构较为完整，心肌纤维排列较为整齐，心肌纤维化面积降低；心脏组织T-AOC、GSH-Px、SOD含量升高，MDA含量降低；ATM、ATR通路相关蛋白表达均显著下调（P < 0.05）。结论 黄精对自然衰老大鼠心脏具有较好的保护作用，其作用可能与抑制DNA损伤应答ATM、ATR通路有关。

Abstract Objective：To observethe cardioprotection of Rhizoma Polygonati（RP） in natural aging rat on the regulation of ataxia-telangiectasia mutated gene（ATM）、ATM and Rad3-related kinase (ATR) mediated DNA?damage response pathway. Methods：16 SD rats aged 2 months were selected as the youth group. another 64 SD rats aged 18 months were randomly divided into 4 groups：an old group，a RP- low，a RP-medium and a RP-high dose group，with 16 rats in each group.The RP-low，RP-medium and RP- high dose groups were administered of RP (1，2，4 g/kg) by gavage，the old and young groups were given the same amount of distilled water once a day for 12 weeks. At week 4 and 12，eight rats from each group were sacrificed?under anesthesia and hearts were isolated.Then cardiac?weight?index(CI) were measured and the histopathologic observations and myocardial?fibrosis?was assessed.The contents of total antioxidant capacity (T-AOC)，glutathione peroxidase (GSH-Px)，superoxide dismutase (SOD) and malondialdehyde (MDA) were measured，and the expression of ATM、ATR-related protein?in cardiac tissue?were detected. Results：The rats in old group had disordered heart tissue with swollen myocardial cells, widened muscle gap?with?increasing week?age. Myocardial?fibers?were?arranged irregularly and broken，and the?fibrosis?area?was?increased .The content of GSH-Px was decreased while MDA was increased；the expression of Chk1 was also up-regulated (P<0.05). In week 4 or 12，compared to the young group，the CI was reduced，and the contents of T-AOC、SOD 、GSH-Px were decreased while MDA was increased；the expression of ATM、ATR-related proteins were all significantly up-regulated in cardiact tissue of old group(P<0.05).After RP treatment，tthe CI was elevated，the?structure?of?cardiomyocytes were intact and the?myocardial?fibers were?arranged?neatly，the?fibrosis?area?was?lowered.?The contents of T-AOC 、GSH-Px、SOD were increased while MDA was decreased.The expression of ATM、ATR -related proteins were significantly down-regulated in cardiac tissue(P<0.05). Conclusion：RP could protect the heart in natural aging rats，and its mechanism may be related to the regulation of DNA damage response ATM、ATR signaling pathway.

国家自然科学基金委员会青年科学基金项目（81403445）：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，负责人：秦臻。国家自然科学基金委员会地区科学基金项目（81860872）：Pink1/Parkin 介导的线粒体自噬对EPCs衰老的作用及黄精的调控机制；负责人：秦臻。国家自然科学基金委员会地区科学基金项目（82360864）：黄精调控内质网应激-自噬通路延缓内皮祖细胞衰老作用的研究，负责人：秦臻。