Gao Jie, Yang Guoqing, Pi Rongbiao, Li Ruifang, Wang Ping, Zhang Huijie, Le Kang, Chen Shaorui, Liu Peiqing
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
Transl Res. 2008 Feb;151(2):79-87. doi: 10.1016/j.trsl.2007.11.005. Epub 2007 Dec 28.
Tanshinone IIA (TSN) is a monomer extracted from the Chinese herb Danshen. In this study, we examined the effect of Tanshinone IIA on adriamycin (ADR)-induced apoptosis in neonatal rat cardiomyocytes and underlying molecular mechanisms. Primary cultured cardiomyocytes were treated with 1 micromol/L of adriamycin for 24 h with or without pretreatment with Tanshinone IIA (0.5-2 micromol/L) for 2 h. 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst staining, and flow cytometry measurement were used to assess cell viability and apoptosis. Fluorescent probes 2',7'-dichlorofluorescein diacetate and dihydroethidium were used to detect the production of reactive oxygen species. Western blotting was used to evaluate the expression of Bcl-2 and Bax proteins. Adriamycin significantly induced apoptosis in cardiomyocytes. Tanshinone IIA (0.5-2 micromol/L) ameliorated apoptosis induced by adriamycin in a dose-dependent manner. Tanshinone IIA (2 micromol/L) markedly attenuated adriamycin-induced reactive oxygen species production. Western blotting revealed that Tanshinone IIA prevented the adriamycin-mediated reduction of the ratio of Bcl-2/Bax. In conclusion, Tanshinone IIA significantly inhibits adriamycin-induced cardiomyocyte apoptosis in a dose-dependent manner, and this effect is at least partly caused by its antioxidant properties.
丹参酮IIA(TSN)是从中药丹参中提取的一种单体。在本研究中,我们研究了丹参酮IIA对阿霉素(ADR)诱导的新生大鼠心肌细胞凋亡的影响及其潜在的分子机制。原代培养的心肌细胞用1微摩尔/升阿霉素处理24小时,同时或不预先用丹参酮IIA(0.5 - 2微摩尔/升)处理2小时。采用3 -(4,5 - 二甲基噻唑 - 2 - 基)- 2,5 - 二苯基四氮唑溴盐(MTT)法、Hoechst染色和流式细胞术检测来评估细胞活力和凋亡情况。使用荧光探针2',7' - 二氯荧光素二乙酸酯和二氢乙锭检测活性氧的产生。采用蛋白质免疫印迹法评估Bcl - 2和Bax蛋白的表达。阿霉素显著诱导心肌细胞凋亡。丹参酮IIA(0.5 - 2微摩尔/升)以剂量依赖的方式改善了阿霉素诱导的凋亡。丹参酮IIA(2微摩尔/升)显著减弱了阿霉素诱导的活性氧产生。蛋白质免疫印迹显示丹参酮IIA阻止了阿霉素介导的Bcl - 2/Bax比值降低。总之,丹参酮IIA以剂量依赖的方式显著抑制阿霉素诱导的心肌细胞凋亡,且这种作用至少部分是由其抗氧化特性引起的。