Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing City, JiangSu province, China.
Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing City, JiangSu province, China.
Life Sci. 2019 Dec 15;239:117016. doi: 10.1016/j.lfs.2019.117016. Epub 2019 Oct 31.
The current study aimed to investigate the effects of tetramethylprazine (TMP) on myocardial ischemia/reperfusion (MI/R) injury and its underlying mechanisms. MI/R rat model and hypoxia/reoxygenation (H/R) cardiomyocytes model were established. CK level and LDH activity were detected to evaluate MI/R and H/R injury. Cell viability was determined by cell counting kit-8 (CCK-8) assay. Cell apoptosis were identified by flow cytometry and autophagy were detected by western blot. Treatment with TMP significantly reduced CK level and LDH activity and decreased myocardial infarct size in MI/R rats. TMP reduced autophagy dysfunction induced by MI/R. Moreover, TMP treatment decreased H/R-induced injury and attenuated autophagy dysfunction in cardiomyocytes. Inhibiting autophagic flux with chloroquine (CQ) decreased the cardioprotection exerted by TMP in vivo and in vitro. Additionally, the effects of TMP on the modulation of autophagy were inhibited by LY294002 (a PI3K inhibitor) in H/R cardiomyocytes. Our findings suggested TMP exerted cardioprotection against MI/R injury by decreasing Beclin-1 associated autophagy dysfunction through PI3K pathway.
本研究旨在探讨川芎嗪（TMP）对心肌缺血再灌注（MI/R）损伤的影响及其作用机制。建立 MI/R 大鼠模型和缺氧/复氧（H/R）心肌细胞模型。通过细胞计数试剂盒-8（CCK-8）测定法检测 CK 水平和 LDH 活性来评估 MI/R 和 H/R 损伤。通过流式细胞术鉴定细胞凋亡，通过 Western blot 检测自噬。TMP 处理可显著降低 MI/R 大鼠的 CK 水平和 LDH 活性，并减少心肌梗死面积。TMP 减轻了 MI/R 诱导的自噬功能障碍。此外，TMP 处理可减轻 H/R 诱导的损伤并减轻心肌细胞中的自噬功能障碍。用氯喹（CQ）抑制自噬流可降低 TMP 在体内和体外的心脏保护作用。此外，在 H/R 心肌细胞中，LY294002（一种 PI3K 抑制剂）抑制了 TMP 对自噬的调节作用。我们的研究结果表明，TMP 通过减少 Beclin-1 相关的自噬功能障碍来发挥对 MI/R 损伤的心脏保护作用，其机制与 PI3K 通路有关。
