Tetramethylprazine attenuates myocardial ischemia/reperfusion injury through modulation of autophagy.

Autor: Zuo Z; Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing City, JiangSu province, China., Zuo PF; Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing City, JiangSu province, China., Sheng ZL; Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing City, JiangSu province, China., Wang X; Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing City, JiangSu province, China., Ding JD; Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing City, JiangSu province, China. Electronic address: dingjiandong@163.com., Ma GS; Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing City, JiangSu province, China. Electronic address: genshan_ma@163.com.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2019 Dec 15; Vol. 239, pp. 117016. Date of Electronic Publication: 2019 Oct 31.
DOI: 10.1016/j.lfs.2019.117016
Abstrakt: 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.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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