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| Although many studies have been performed to elucidate the molecular mechanisms of heart failure, an effective pharmacological therapy to protect cardiac tissues from severe loss of contractile function associated with heart failure after acute Myocardial Infarction(MI)has yet to be developed. We examined the cardioprotective effects of S-Propargyl-L-cysteine (SPRC, also named as ZYZ-802), a novel hydrogen sulfide donor with potent antioxidant and anti-apoptotic activities in diabetes mellitus (DM) rat models of heart failure.SPRC was systemically delivered to rats 7 days before MI and 6 weeks after MI at different doses (15, 30, 60mg/kg). Cardiac function was assessed by hemodynamic measurements. The expression of proinflammatory cytokines, apoptosis-related molecules and the markers of adverse ventricular remodeling were measured using RT-PCR and Western blot. Treatment with SPRC significantly improved cardiac function, in particular by increasing dP/dt. Simultaneously, the expression of the pro-inflammatory cytokines TNF-α and IL-1 was markedly reduced in the treatment group compared with the MI group. In addition， SPRC-treated tissues displayed decreased expression of Bax, caspase-3, and caspase-9 and increased expression of Bcl-2, which was in part due to the promotion of Akt phosphorylation. These data demonstrated that SPRC possesses potent cardioprotective effects against cardiac injury in DM rat modelsof heart failure, which is mediated, at least in part, by suppression of the inflammatory and cell apoptosis responses. |
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| Keywords:SPRC; diabetes mellitus; antioxidant; inflammatory; apoptosis; cardioprotective effects |
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