Protective and biogenesis effects of sodium hydrosulfide on brain mitochondria after cardiac arrest and resuscitation

摘要

Mitochondrial dysfunction plays a critical role in brain injury after cardiac arrest and cardiopulmonary resuscitation (CPR). Recent studies demonstrated that hydrogen sulfide (H_2S) donor compounds preserve mitochondrial morphology and function during ischemia-reperfusion injury. In this study, we sought to explore the effects of sodium hydrosulfide (NaHS) on brain mitochondria 24 h after cardiac arrest and resuscitation. Male Sprague-Dawley rats were subjected to 6 min cardiac arrest and then resuscitated successfully. Rats received NaHS (0.5 mg/kg) or vehicle (0.9% NaCl, 1.67 ml/kg) 1 min before the start of CPR intravenously, followed by a continuous infusion of NaHS (1.5 mg/kg/h) or vehicle (5 ml/ kg/h) for 3 h. Neurological deficit was evaluated 24 h after resuscitation and then cortex was collected for assessments. As a result, we found that rats treated with NaHS revealed an improved neurological outcome and cortex mitochondrial morphology 24 h after resuscitation. We also observed that NaHS therapy reduced intracellular reactive oxygen species generation and calcium overload, inhibited mitochondrial permeability transition pores, preserved mitochondrial membrane potential, elevated ATP level and ameliorated the cytochrome c abnormal distribution. Further studies indicated that NaHS administration increased mitochondrial biogenesis in cortex at the same time. Our findings suggested that administration of NaHS 1 min prior CPR and followed by a continuous infusion ameliorated neurological dysfunction 24 h after resuscitation, possibly through mitochondria preservation as well as by promoting mitochondrial biogenesis.