Wang Yahui, Wang Qiangli, Zhang Lu, Ke Zunli, Zhao Yuanyuan, Wang Dongshan, Chen Hui, Jiang Xi, Gu Ming, Fan Shengjie, Huang Cheng
Drug Discovery Lab, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Biochem Biophys Res Commun. 2017 Aug 19;490(2):231-238. doi: 10.1016/j.bbrc.2017.06.027. Epub 2017 Jun 9.
Coptisine is a natural occurring isoquinoline alkaloid isolated from the traditional Chinese medicinal herb Rhizoma coptidis. Coptisine has been reported to have protective effects on reperfusion injury in cardiomyocytes, however, the underlying mechanism remains uncertain. Here, we used a hypoxia/reoxygenation (H/R)-treated H9c2 cell model to study the protective effects of coptisine on cardiomyocyte. The results showed that NaSO induced hypoxia/reoxygenation model increased apoptosis and up-regulated autophagy marker LC3-II and cleaved Caspase-3, Beclin1 and Sirt1 levels. Coptisine treatment increased cell survival, inhibited apoptosis, and reduced the protein level of LC3-II, cleaved Caspase-3, Beclin1 and Sirt1. Further, we showed that coptisine combined with chloroquine (CQ), the inhibitor of autolysosome, reduced LC3-II, suggesting that coptisine may inhibit autophagosome formation than induction of autolysosome in the autophagy events. Our results indicate that coptisine may protect cardiomyocyte damage by H/R through suppressing autophagy. Overall, our study provides a new mechanism for the treatment of coptisine on H/R-induced cardiomyocyte damage and death.
黄连碱是一种从传统中药黄连中分离出的天然异喹啉生物碱。据报道，黄连碱对心肌细胞的再灌注损伤具有保护作用，然而，其潜在机制仍不明确。在此，我们使用缺氧/复氧（H/R）处理的H9c2细胞模型来研究黄连碱对心肌细胞的保护作用。结果显示，NaSO诱导的缺氧/复氧模型增加了细胞凋亡，并上调了自噬标志物LC3-II以及切割的Caspase-3、Beclin1和Sirt1的水平。黄连碱处理提高了细胞存活率，抑制了细胞凋亡，并降低了LC3-II、切割的Caspase-3、Beclin1和Sirt1的蛋白水平。此外，我们发现黄连碱与自溶酶体抑制剂氯喹（CQ）联合使用可降低LC3-II水平，这表明在自噬过程中，黄连碱可能抑制自噬体形成而非诱导自溶酶体。我们的结果表明，黄连碱可能通过抑制自噬来保护心肌细胞免受H/R损伤。总体而言，我们的研究为黄连碱治疗H/R诱导的心肌细胞损伤和死亡提供了一种新机制。
