药学学报, 2014, 49(8): 1117-1123
引用本文:
孟晨, 袁彩华, 张晨晨, 温明达, 高艳红, 丁小余, 张赢予, 张朝. 麦冬皂苷D通过减轻内质网应激对阿霉素所致心肌损伤产生保护作用[J]. 药学学报, 2014, 49(8): 1117-1123.
MENG Chen, YUAN Cai-hua, ZHANG Chen-chen, WEN Ming-da, GAO Yan-hong, DING Xiao-yu, ZHANG Ying-yu, ZHANG Zhao. Ophiopogonin D protects cardiomyocytes against doxorubicin-induced injury through suppressing endoplasmic reticulum stress[J]. Acta Pharmaceutica Sinica, 2014, 49(8): 1117-1123.

麦冬皂苷D通过减轻内质网应激对阿霉素所致心肌损伤产生保护作用
孟晨1, 袁彩华1, 张晨晨1, 温明达1, 高艳红1,2, 丁小余1, 张赢予3,4, 张朝1,2
1. 南京师范大学生命科学学院, 江苏省分子医学生物技术重点实验室、江苏省超分子医用材料及应用重点实验室, 江苏 南京 210023;
2. 南京医科大学, 江苏省心血管病转化医学协同创新中心, 江苏 南京 210029;
3. 江苏大学附属人民医院, 分子生物学和转化医学研究所, 江苏 镇江 212002;
4. 长春医学高等专科学校临床医学系, 吉林 长春 130013
摘要:
研究麦冬皂苷D(ophiopogonin D,OP-D) 对阿霉素(doxorubicin,DOX) 所致心肌损伤的保护作用。体外培养H9c2细胞,采用MTT法检测细胞毒性,MitoTracker探针法测定细胞内线粒体中活性氧(reactive oxygen species,ROS) 含量,实时定量PCR和Western blotting分别检测ATF6α,GRP78和CHOP的mRNA及其蛋白表达。结果表明,DOX可诱导H9c2细胞内质网应激相关蛋白的表达量显著上升,并导致细胞活性氧ROS含量增加,细胞活力下降。而OP-D预处理可部分逆转DOX引起的上述变化,siRNA干扰促凋亡转录因子CHOP或抗氧化剂NAC预处理也有类似效应。此外,OP-D可明显减轻DOX所致小鼠心脏超微结构异常。这些结果说明,OP-D通过降低DOX诱导的ROS累积,进而缓解内质网应激而对心肌产生保护作用。
关键词:    阿霉素      麦冬皂苷D      心肌细胞      内质网应激     
Ophiopogonin D protects cardiomyocytes against doxorubicin-induced injury through suppressing endoplasmic reticulum stress
MENG Chen1, YUAN Cai-hua1, ZHANG Chen-chen1, WEN Ming-da1, GAO Yan-hong1,2, DING Xiao-yu1, ZHANG Ying-yu3,4, ZHANG Zhao1,2
1. Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Jiangsu Key Laboratory for Supermolecular Medicinal Materials and Applications, College of Life Science, Nanjing Normal University, Nanjing 210023, China;
2. Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 210029, China;
3. Institute of Molecular Biology and Translational Medicine, the Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, China;
4. Department of Clinical Medicine, Changchun Medical College, Changchun 130013, China
Abstract:
This study aimed to examine whether ophiopogonin D (OP-D) is capable of protecting cardiomyocytes against DOX-induced injury and the mechanisms involved. H9c2 cells were cultured. MTT assay was used to evaluate cell viability and toxicity. Mito-tracker as fluorescence probe was used to measure ROS content raised from mitochondria. The mRNA and protein expression of ATF6α, GRP78 and CHOP were analyzed using real-time PCR and Western blotting, respectively. The results showed that a significant endoplasmic reticulum stress (ERS) was induced upon exposure of H9c2 cells to DOX as indicated by the increase in the expression of ERS related proteins, which was paralleled with the accumulation of reactive oxygen species (ROS) and decrease in the viability of H9c2 cells. Whereas, DOX-induced ROS accumulation and up-regulation of ERS related proteins were partially abolished by pretreatment with OP-D. Consequently, a DOX-induced ERS was mitigated by application of OP-D. Similarly, DOX-induced decrease in cell viability was partially attenuated by either inhibiting CHOP or pretreatment with N-acetylcysteine (NAC), an antioxi-dant. Moreover, cardiac ultrastructural abnormalities seen in mouse receiving DOX injections were obviously ameliorated by pretreatment of OP-D. Taken together, the present study proved that OP-D protects cardiomyocytes against DOX-induced injury, at least in part, through reducing ROS accumulation and alleviating ERS.
Key words:    doxorubicin    ophiopogonin D    cardiomyocyte    endoplasmic reticulum stress   
收稿日期: 2014-02-27
基金项目: 国家自然科学基金资助项目(30570662,30871228,31171302);江苏省分子医学生物技术重点实验室开放基金资助项目(2011MMBKF04).
通讯作者: 张赢予 Tel/Fax:86-511-85234387,E-mail:zhang_yingyu@163.com;张朝 Tel:86-25-85891915,Fax:86-25-85891702,E-mail:zhangzhao@njnu.edu.cn
Email: zhang_yingyu@163.com;zhangzhao@njnu.edu.cn
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