Feng Jun, Li Shusheng, Chen Huawen
Department of Emergency Medicine, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
Exp Biol Med (Maywood). 2016 Dec;241(18):2042-2048. doi: 10.1177/1535370216660634. Epub 2016 Jul 28.
The fat-soluble diterpenoids tanshinone IIA (TSA) is the major active element of Danshen, which has widespread cardioprotective effect. However, the mechanism of its beneficial effect on cardiomyocytes has not been fully investigated. Here, we aim to demonstrate that TSA ameliorates apoptosis of cardiomyocytes activated by endoplasmic reticulum stress (ERS). Primary cultures of neonatal rat cardiomyocytes are used, in which ERS-mediated apoptosis is induced by tunicamycin (Tm). Apoptosis of cardiomyocytes are detected by Hoechst staining and caspase 3 activity analysis. Protein expression of ERS markers are detected by Western blot, and level of miroRNA-133 (miR-133) is detected by real-time polymerase chain reaction. Tm treatment significantly triggers the apoptosis and ERS of cardiomyocytes. TSA dramatically ameliorates apoptosis and ERS of cardiomyocytes induced by Tm. Interestingly, level of miR-133 is reduced by Tm treatment, which is reversed by TSA. The cardioprotective effect of TSA on apoptosis and ERS of cardiomyocytes is blocked by anti-miR-133. These results suggest that TSA protects cardiomyocytes through ameliorated ERS-mediated apoptosis, which may be resulted from upregulation of miR-133.
脂溶性二萜类化合物丹参酮IIA（TSA）是丹参的主要活性成分，具有广泛的心脏保护作用。然而，其对心肌细胞有益作用的机制尚未得到充分研究。在此，我们旨在证明TSA可改善内质网应激（ERS）激活的心肌细胞凋亡。使用新生大鼠心肌细胞原代培养物，其中衣霉素（Tm）诱导ERS介导的凋亡。通过Hoechst染色和半胱天冬酶3活性分析检测心肌细胞凋亡。通过蛋白质印迹法检测ERS标志物的蛋白质表达，并通过实时聚合酶链反应检测微小RNA-133（miR-133）的水平。Tm处理显著触发心肌细胞的凋亡和ERS。TSA显著改善Tm诱导的心肌细胞凋亡和ERS。有趣的是，Tm处理使miR-133水平降低，而TSA可使其逆转。TSA对心肌细胞凋亡和ERS的心脏保护作用被抗miR-133阻断。这些结果表明，TSA通过改善ERS介导的凋亡来保护心肌细胞，这可能是由于miR-133上调所致。
