23-羟基白桦酸对阿霉素所致H9c2心肌细胞损伤的保护作用及抗氧化机制研究  

Protective effect of 23-hydroxybetulinic acid against doxorubicin-induced cardiotoxicity through the antioxidant activity in H9c2 cells

作　　者：郝刚[1] 周芳[1] 刘嘉莉[1] 王广基[1] 桑国卫[2] 叶文才[3] 

机构地区：[1]中国药科大学药物代谢动力学重点实验室 [2]中国药品生物制品检定所,北京100050 [3]暨南大学中药及天然药物研究所

出　　处：《中国临床药理学与治疗学》2012年第7期736-743,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金："十一五"重大新药创制专项资助(2009ZX09304-001);国家自然科学基金资助(30801411);中央高校基本科研业务费专项资金资助(JKY2009012)

摘　　要：目的:基于细胞水平研究23-羟基白桦酸(23-HBA)对阿霉素(DOX)心肌损伤的保护作用并探讨其抗氧化机制。方法:采用H9c2心肌细胞,考察对照组、DOX组、23-HBA组及23-HBA联合DOX组给药后心肌细胞形态学变化,测定细胞体积及蛋白含量,Real time-PCR测定心钠素(ANP)、脑钠素(BNP)的mRNA水平。考察心肌细胞内Caspase-3活性及Hoechst荧光染色后细胞核形态从而评价细胞凋亡水平。利用DCFH荧光探针测定细胞ROS水平,同时检测细胞内脂质过氧化物(MDA)生成量,评价细胞氧化损伤水平,寻找23-HBA心肌保护的可能机制。结果:5μmol/L DOX诱导心肌细胞肥大,表现为细胞体积增大,蛋白含量增多,并显著上调细胞内ANP与BNP的mRNA水平,提高细胞内Caspase-3活性,导致细胞凋亡。23-HBA与DOX联合用药后,浓度依赖地降低DOX给药后心肌细胞内ROS水平,清除脂质过氧化物MDA,逆转DOX诱导的心肌肥大、心肌损伤标志物上调、心肌细胞凋亡等过程。结论:23-HBA可通过其抗氧化作用降低DOX所致的心肌损伤。AIM： To investigate the potential protective effects of 23-hydroxybetulinic acid （23-HBA） on doxorubicin （DOX）-induced car- diotoxicity and the underlying mechanisms. METHODS： H9c2 ceils were treated with DOX, 23-HBA, or their combinations, cell size and protein content were determined to evaluate the cardiac hypertrophy induced by DOX. Expres- sion of ANP and BNP mRNA were studied by Real-time PCR. D（3X-induced caspase-3 activa- tion and apoptosis were further studied. Oxida- tive stress and lipid peroxidation were deter- mined to evaluate the potential mechanism of the cardioprotective effect of 23-HBA. RESULTS： 23-HBA remarkably reduced the mRNA level of ANP and BNP induced by DOX, and reversed the cardiac hypertrophy caused by DOX treat- ment. Caspase-3 activity also significantly re- duced when combined treated with 23-HBA and DOX compared to DOX treatment. Further studies showed that 23-HBA exerted its cardio- protective effect on DOX through decreasing the intracellular ROS and MDA amount. CONCLU- SION： 23-HBA protected H9c2 cells against the cardiotoxicity of DOX, and the reduction of oxy- gen free radicals in cardiac myocytes may be the underlying mechanism mediating the protective effect of 23-HBA.

关 键 词：23-羟基白桦酸 阿霉素 心肌损伤 

分 类 号：R965.2[医药卫生—药理学]