Hydrogen sulfide attenuates spatial memory disorder induced by cerebral anoxia via antioxidation in mice / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVETo investigate effects of exogenous hydrogen sulfide ( H2 S) on the spatial memory disorder induced by cerebral anoxia in mice and explore related mechanism.METHODS Sodium nitrite (NaNO2) 120 mg·kg-1 was sc given to mice for4 d in model group.Sodium hydrosulfide (NaHS) 1 mg·kg-1 was ip given and NaNO2 120 mg·kg-1 simultaneously was sc given to mice for4 d in NaHS group.All drugs were given to mice immediately after Morris water maze experiment every day and escape latency.The number of crossings over the target area (NCTA) and search time in target quadrant (STTQ) were recorded.The activity of superoxide dismutase (SOD) and malondialdehyde (MDA) level in the brain was determined with colorimetry.The morphological alterations in hippocampus slices were assessed by microscope.RESULTSOn the third and fourth days in Morris water maze experiment,compared with ( 16.1 ±9.6)s and ( 11.1 ±6.2)s in normal control group,the escape latency in model group was longer,(26.0 ±7.3)s(P＜0.05) and (23.3 ±8.7)s(P＜0.01).On the fifth day,compared with 7.2 ± 1.6 and (28 ± 8) s in normal control group NCTA and STTQ in model group were 4.1 ± 1.9and (20 ± 8 ) s ( P ＜ 0.05 ),and they were obviously less.Compared with normal control group,SOD activity and M DA content of mice in model group were reduced by 12.6％ (P ＜ 0.01 ) and increased by 43.9％ (P ＜ 0.01 ),respectively.The neuron degenerative changes including karyopyknosis,dark cytoplasm and irregular pyramidal layer were observed in model group.On the third and fourth day,compared with model group,the escape latency in NaHS group was shorter,(17.9 ±7.0)s and (15.8 ±8.5)s (P＜0.05).Compared with model group,NCTA and STTQ in NaHS group increased to 6.7 ± 2.5 and ( 30 ± 9) s ( P ＜ 0.01 ).SOD activity and MDA content in NaHS group were increased by 8.9％ ( P ＜ 0.05 ) and reduced by 29.6％ ( P ＜ 0.01 ),respectively.Neuron degeneration was significantly attenuated in NaHS group (P ＜ 0.01 ).CONCLUSIONNaHS can attenuate the spatial memory disorder induced by cerebral anoxia and the mechanism may be related to the antioxidation effect and alleviation of neuron damage of H2S.