摘要
目的观察模拟绝经及D-半乳糖模型小鼠空间认知的改变,评价雌激素保护海马神经元功能的分子机制。方法成年雌性C57BL/6小鼠双侧卵巢切除(OVX)并皮下注射D-半乳糖100mg/kg造模。雌激素替代治疗(ERT)组腹腔注射17β-雌二醇(E2)50μg/kg。造模与ERT共8周。Morris水迷宫测试空间学习记忆功能,试剂盒检测雌激素与氧化应激酶。免疫组化染色8-氧鸟嘌呤脱氧核苷(8-oxo-dG),Western blotting检测脑海马MTH1表达。结果模型组血中E2水平仅为假手术组的1/5(P<0.01),而ERT组明显升高(P<0.01);模型组寻台时间明显延长(P<0.01),ERT组缩短(P<0.05);模型组SOD、GSH-Px明显降低而MDA明显增高(P<0.05),ERT组接近正常。8-oxo-dG作为DNA氧化损伤标志物在模型组海马明显增多,而DNA修复蛋白MTH1表达明显减少(P<0.05),而两者在ERT组恢复正常(P<0.05)。结论雌激素可通过对海马神经元受损DNA的修复及抗氧化作用改善衰老模型的空间认知功能。
Objective To observe the imitation of menopause and the change of spatial cognition in mice administrated with D-galactose and to evaluate the molecular mechanism of estrogen to protect the function of hippocampal neurons.Methods Adult female C57BL/6 mice were bilateral ovariectomy （OVX） and subcutaneously treated with D-galactose （100 mg/kg）. In estrogen replacement therapy（ERT） mice were i.p. administrated with E2 （50 μg/kg）. It took 8 weeks to induce the model and treat with ERT. Morris water maze was used test the function of spatial learning and memory. Estrogen and oxidative stress enzymes were detected by kit. 8-oxo-dG was immunohistochemical stained,and the expression of MTH1 in brain hippocampus was detected by Western blotting.Results The level of E2 in blood in model group was one fifth of that in Sham group（P〈0.01）,and E2 level obviously increased in ERT group; the escape latency significantly prolonged in model group（P〈0.01）,and obviously shortened in ERT group（P〈0.05）. SOD and GSH-Px significantly reduced and MDA obviously increased in model group（P〈0.05）; and approached normal in ERT group. 8-oxo-dG as a DNA oxidative damage marker was obviously increased in the hippocampus of model group. However,the expression of DNA repair protein MTH1 significantly reduced（P〈0.05）,and both of them returned to normal in ERT group（P〈0.05）.Conclusion Estrogen can improve the function of spatial cognition in aging mice model by repairing the DNA damage of hippocampal neurons.
出处
《中国康复理论与实践》
CSCD
2010年第4期324-327,共4页
Chinese Journal of Rehabilitation Theory and Practice
基金
国家重点基础研究发展计划973项目(2007CB507400)
科技部重大新药创制科技专项项目(2009ZX09303)
