Astragalus polysaccharide suppresses doxorubicin-induced cardiotoxicity by regulating the PI3k/Akt and p38MAPK pathways.
Astragalus polysaccharide suppresses doxorubicin-induced cardiotoxicity by regulating the PI3k/Akt and p38MAPK pathways.
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黄芪多糖通过调节 PI3k/Akt 和 p38MAPK 通路抑制阿霉素诱导的心脏毒性。
DOI：
10.1155/2014/674219
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发表时间：
2014
影响因子：
--
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Cao Y;Ruan Y;Shen T;Huang X;Li M;Yu W;Zhu Y;Man Y;Wang S;Li J
背景。阿霉素是一种有效的化疗药物，与急性和慢性心脏毒性有关，这是累积剂量依赖性的。黄芪多糖（Astragalus多糖，APS）是黄芪提取物，具有较强的抗肿瘤和抗肾小球肾炎活性，能有效缓解炎症。然而，APS是否能改善化疗引起的心脏毒性尚不清楚。在此，我们研究了黄芪多糖对阿霉素诱导的心脏毒性的保护作用，并阐明了黄芪多糖保护作用的潜在机制。方法。我们分析了接受阿霉素化疗的癌症患者的心肌损伤，并建立了阿霉素诱导的新生大鼠心肌细胞损伤模型和小鼠心力衰竭模型。通过超声心动图、活性氧（ROS）生成、TUNEL、DNA阶梯和Western blotting观察心肌细胞的细胞存活、氧化应激和炎症信号通路。结果。患者使用化疗药物阿霉素治疗导致心功能障碍。阿霉素降低心肌细胞活力，诱导C57BL/6J小鼠心力衰竭，同时ROS生成和细胞凋亡升高，而APS治疗可减轻这一作用。此外，APS处理后，p38MAPK和Akt的活性都受到了抑制。结论。这些结果表明，APS可以通过调节PI3k/Akt和p38MAPK通路，抑制氧化应激和细胞凋亡，改善阿霉素介导的心脏毒性。
Background. Doxorubicin, a potent chemotherapeutic agent, is associated with acute and chronic cardiotoxicity, which is cumulatively dose-dependent. Astragalus polysaccharide (APS), the extract of Astragalus membranaceus with strong antitumor and antiglomerulonephritis activity, can effectively alleviate inflammation. However, whether APS could ameliorate chemotherapy-induced cardiotoxicity is not understood. Here, we investigated the protective effects of APS on doxorubicin-induced cardiotoxicity and elucidated the underlying mechanisms of the protective effects of APS. Methods. We analyzed myocardial injury in cancer patients who underwent doxorubicin chemotherapy and generated a doxorubicin-induced neonatal rat cardiomyocyte injury model and a mouse heart failure model. Echocardiography, reactive oxygen species (ROS) production, TUNEL, DNA laddering, and Western blotting were performed to observe cell survival, oxidative stress, and inflammatory signal pathways in cardiomyocytes. Results. Treatment of patients with the chemotherapeutic drug doxorubicin led to heart dysfunction. Doxorubicin reduced cardiomyocyte viability and induced C57BL/6J mouse heart failure with concurrent elevated ROS generation and apoptosis, which, however, was attenuated by APS treatment. In addition, there was profound inhibition of p38MAPK and activation of Akt after APS treatment. Conclusions. These results demonstrate that APS could suppress oxidative stress and apoptosis, ameliorating doxorubicin-mediated cardiotoxicity by regulating the PI3k/Akt and p38MAPK pathways.
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影响因子：
--
作者：
Ashour AE;Sayed-Ahmed MM;Abd-Allah AR;Korashy HM;Maayah ZH;Alkhalidi H;Mubarak M;Alhaider A
通讯作者：
Alhaider A
影响因子：
37.8
作者：
Li, K;Sung, RYT;Ng, PC
通讯作者：
Ng, PC
影响因子：
37.8
作者：
Zhu, Wuqiang;Soonpaa, Mark H.;Chen, Hanying;Shen, Weihua;Payne, R. Mark;Liechty, Edward A.;Caldwell, Randall L.;Shou, Weinian;Field, Loren J.
通讯作者：
Field, Loren J.
影响因子：
15.9
作者：
Shen, Tao;Aneas, Ivy;Evans, Sylvia M.
通讯作者：
Evans, Sylvia M.
影响因子：
37.8
作者：
Fisher, PW;Salloum, F;Kukreja, RC
通讯作者：
Kukreja, RC