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

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,10 μmol/kg)、中剂量小鼠组(NM Group,50 μmol/kg)和高剂量小鼠组(NH Group,100 μmol/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(H₂S)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H₂S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H₂S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H₂S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。

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

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, 10 μmol/kg), medium dose group (NM Group, 50μmol/kg) and high dose group (NH Group, 100 μmol/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 (H₂S) 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 H₂S 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 H₂S and MBP in hippocampus of SCA3 mice were also improved in different degrees (P＜0.05). Conclusion: Exogenous NaHS may increase the contents of H₂S 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.