RESUMO
Objective To investigate the effects of exogenous hydrogen sulfide (H2S) on the mitochondrial function during focal cerebral ischemia and the relationship with mitochondrial damage in rats.Methods Eighty male Sprague-Dawley rats,weighing 250-300 g,were randomly divided into 5 groups (n =16 each):sham operation group (group S),cerebral ischemia group (group CI),and high,medium and low dose NaHS groups (NaHS1,NaHS2 and NaHS3 groups).The animals were anesthetized with intraperitoneal chloral hydrate.The focal cerebral ischemia was induced by middle cerebral artery occlusion.Normal saline 1 ml/kg was injected intraperitoneally at 3 h after the model was established.NaHS 2.8,1.4 and 0.7 mg/kg were injected intraperitoneally in NaHS1,NaHS2 and NaHS3 groups,respectively.At 24 h after the model was established,the cerebral infarct volume was determined.The changes in the cerebral infarct volume were observed after administration of NaHS.Cerebral specimens on the ischemic side were obtained for determination of the content of H2S and activity of 3-mercaptopyruvate sulphurtransferase (3MST) in brain tissues.The mitochondria were extracted for determination of the activity and swelling of mitochondrial membrane and changes in the total ATPase,superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA) content.Results Compared with group S,the cerebral infarct volume was significantly enlarged in CI,NaHS1,NaHS2 and NaHS3 groups,the content of H2 S in brain tissues and activity of mitochondrial 3MST were decreased in CI,NaHS2 and NaHS3 groups,the activities of mitochondria,SOD and GSH-Px were significantly decreased,and the swelling of mitochondrial membrane and content of MDA were increased in CI and NaHS3 groups,the total ATPase activity was decreased in CI group,and SOD activity was decreased in NaHS1 and NaHS2 groups.Compared with CI group,the cerebral infarct volume was significantly reduced,the content of H2 S in brain tissues and activity of mitochondrial 3MST were increased,the activities of mitochondria,total ATPase,SOD and GSH-Px were increased,the swelling of mitochondrial membrane was reduced,and the content of MDA was decreased in NaHS1 and NaHS2 groups.Conclusion The mechanism by which exogenous H2 S mitigates focal cerebral ischemia is related to enhanced anti-oxidant activity of mitochondria and reduced mitochondrial damage in rats.
RESUMO
ObjectiveTo evaluate the effect of aminooxyacetic acid on focal cerebral ischemia injury in rats.MethodsEighty healthy male SD rats aged 2.5 month weighing 250-280 g were randomly divided into five groups( n ＝ 16 each):sham operation group(group S),cerebral ischemia group(group Ⅰ),aminooxoacetic acid low,medium and high dose groups(groups AL,AM and AH ).Focal cerebral ischemia was induced by occlusion of middle cerebral artery using a nylon thread with rounding tip which was inserted into right internal carotid artery in groups I,AL,AM and AH.Intraperitoneal amincoxoacetic acid 25,50 and 100 μmol/kg were administered at 3 h of ischemia in groups AL,AM and AH respectively,while equal volume of normal saline 1 ml/kg were injected in groups S and I.Neurological function was assessed and scored (0＝ no deficit,4＝ unable to move,unconscious) in 8 rats at 21 h after aminooxyacetic acid administration in each group.The animals were then sacrificed and the brains were removed for determination of the cystathionine beta-synthase (CBS) activities in cortex,hippocampus and striatum corpora.The other eight rats of each group were sacrificed at 21 h after amincoxoacetic acid administration for determination of the cerebral infarct volume.ResultsCompared with group S,the neurological deficit scores and the CBS activities in cortex and hippocampus were significantly increased,the infarct volumes were significantly enlarged in group Ⅰ ( P < 0.05).Compared with group Ⅰ,the neurological deficit scores and the CBS activities in cortex and hippocampus were significantly decreased,the cerebral infarct volumes were significantly reduced in groups AM and AH (P < 0.05).There was no significant difference in the above-mentioned variables between groups AL and Ⅰ.ConclusionAminooxoacetic acid can reduce focal cerebral ischemia injury by decreasing CBS activity and reducing H2 S production in rats.