Int J Med Sci 2021; 18(12):2716-2724. doi:10.7150/ijms.59411

Research Paper

A novel Danshensu/tetramethylpyrazine protects against Myocardial Ischemia Reperfusion Injury in rats

Jinghao Wang2#, Kai Fan3#, Cong He1, Qingyang Wang1, Qianhui Zhang1, Wei Huang1✉

1. Department of Pharmacology, Harbin Medical University-Daqing, Daqing, 163319, China.
2. Department of Pharmacy, the First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
3. Department of Pathophysiology, Harbin Medical University-Daqing, Daqing, 163319, China.
#These authors contributed equally to this study.

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Citation:
Wang J, Fan K, He C, Wang Q, Zhang Q, Huang W. A novel Danshensu/tetramethylpyrazine protects against Myocardial Ischemia Reperfusion Injury in rats. Int J Med Sci 2021; 18(12):2716-2724. doi:10.7150/ijms.59411. Available from https://www.medsci.org/v18p2716.htm

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Abstract

A new Danshensu/tetramethylpyrazine derivative (ADTM) with cardio-protection effects such as antioxidant, arterial relaxation, pro-angiogenesis and antiplatelet activities. Platelet activating factor receptor (PAFR) plays a key role in myocardial ischemia reperfusion (MIR) injury. This study aims to investigate the protective role of ADTM in MIR injury and clarify the potential role of PAFR. We measured the effects of ADTM on MIR injury in rats in vivo and hypoxia re-oxygenation (HR) injury in neonatal rat ventricular myocytes (NRVMs) in vitro. The results show that ADTM can significantly improve the IR-induced decline in heart function as increasing EF and FS, and restore the decreased cardiac hemodynamic parameters (LVSP, ± dp/dt max) and increased the level of LVEDP, decrease the infarct size of damaged myocardium and lactate dehydrogenase (LDH) activity in serum. Additionally, ADTM inhibits cardiomyocytes apoptosis, caspase-3 activity, and inflammatory response as well as down-regulates the MIR-induced IL-1β and TNFα production. Next, PAFR expression was significantly down-regulated in cardiomyocytes of MIR model in vivo and in vitro after treated with ADTM compare to IR group. At the same time, ADTM and PAFR small interfering RNA (siRNA) could inhibit cardiomyocytes apoptosis and inflammation during HR, while PAF presents the opposite effect. Furthermore, the above effects of PAF in HR induced cardiomyocytes were reversed by co-treatment of ADTM. Our findings demonstrate for the first time that ADTM protects against MIR injury through inhibition of PAFR signaling, which provides a new treatment for MIR.

Keywords: ADTM, ischemia reperfusion, PAFR, apoptosis, inflammation