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丹参酮IIA保护新生大鼠心肌细胞免受阿霉素诱导的凋亡。

Tanshinone IIA protects neonatal rat cardiomyocytes from adriamycin-induced apoptosis.

作者信息

Gao Jie, Yang Guoqing, Pi Rongbiao, Li Ruifang, Wang Ping, Zhang Huijie, Le Kang, Chen Shaorui, Liu Peiqing

机构信息

Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.

出版信息

Transl Res. 2008 Feb;151(2):79-87. doi: 10.1016/j.trsl.2007.11.005. Epub 2007 Dec 28.

Abstract

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.

摘要

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。

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