硫氢化钠对脊髓小脑共济失调3型小鼠海马MBP及学习记忆的影响

Effects of NaHS on MBP and learning and memory in hippocampus of mice with spinocerebellar ataxia

目的:探讨硫氢化钠(NaHS)对脊髓小脑共济失调3型(SCA3)小鼠海马神经元髓鞘碱性蛋白(MBP)及学习记忆的影响及其治疗意义。方法:随机挑选12只雄性正常野生型小鼠(WT)作为正常对照组(NC Group),然后将48只SCA3小鼠随机分为SCA3模型组(M Group)、低剂量小鼠组(NL Group,10μmol/kg)、中剂量小鼠组(NM Group,50μmol/kg)和高剂量小鼠组(NH Group,100μmol/kg),每组12只,用药组每日腹腔注射一次,连续4周。通过Morris水迷宫比较不同剂量NaHS干预前后SCA3小鼠学习记忆能力的变化,分光光度法测定海马内硫化氢(H 2 S)含量,免疫组化技术检测髓鞘碱性蛋白(MBP)的表达差异,并借助电镜观察各组小鼠神经元髓鞘形态学变化。结果:与对照组小鼠比较,SCA3小鼠的学习记忆能力显著下降(P<0.05),海马内H 2 S含量降低(P<0.05),有髓神经纤维MBP表达量也降低(P<0.05),经过不同剂量的外源性NaHS治疗后,学习记忆能力有不同程度改善(P<0.05);且SCA3小鼠海马H 2 S和MBP含量也有不同程度提高(P<0.05)。结论:外源性NaHS可能通过提高SCA3小鼠大脑海马的H 2 S含量和MBP含量增加,对神经元细胞产生一定的保护作用,进而提高SCA3小鼠的学习记忆能力,为寻求SCA3的治疗提供新的思路,同时为临床SCA3患者的营养支持及治疗提供方向。

Objective:To investigate the effects of exogenous NaHS on myelin basic protein(MBP)and learning and memory of hippocampal neurons in mice with spinocerebellar ataxia type 3(SCA3)and its therapeutic significance.Methods:Twelve male normal mice were randomly selected as normal control group(NC Group),and 48 SCA3 mice were randomly selected as SCA3 model group(M Group),low dose group(NL Group,10μmol/kg),medium dose group(NM Group,50μmol/kg)and high dose group(NH Group,100μmol/kg),12 rats in each group.The drug treated groups were injected with NaHS intraperitoneally once a day for 4 weeks.The changes of learning and memory ability of SCA3 mice before and after the intervention of different doses of NaHS were determined by Morris water maze,the content of hydrogen sulfide(H 2 S)in hippocampus was measured by spectrophotometry,the expression of MBP was detected by immunohistochemistry,and the morphological changes of neuron myelin sheath were observed by electron microscope.Results:Compared with the control group,the learning and memory ability of SCA3 mice was decreased significantly(P<0.05),and the content of H 2 S in hippocampus was decreased(P<0.05).After different doses of exogenous NaHS treatment,the learning and memory ability was improved in different degrees(P<0.05),and the contents of H 2 S and MBP in hippocampus of SCA3 mice were also improved in different degrees(P<0.05).Conclusion:Exogenous NaHS may increase the contents of H 2 S and MBP in the hippocampus of SCA3 mice,which may have a protective effect on the neurons,and then improve the learning and memory ability of SCA3 mice,and provide a new idea for the treatment of SCA3.