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.