基础医学与临床 ›› 2017, Vol. 37 ›› Issue (7): 982-987.

• 研究论文 • 上一篇    下一篇

雌激素替代治疗对中年卵巢切除大鼠大脑白质、海马内髓鞘及Lingo-1蛋白的影响

李桃1,罗艳敏1,肖倩1,綦英强2,晁凤蕾1,黄维1,唐勇1   

  1. 1. 重庆医科大学
    2. 重庆医科大学基础医学院干细胞与组织工程学研究室
  • 收稿日期:2016-12-29 修回日期:2017-04-26 出版日期:2017-07-05 发布日期:2017-06-23
  • 通讯作者: 唐勇 E-mail:ytang062@163.com
  • 基金资助:
    国家自然科学基金面上项目;重庆市首批“百名学术学科领军人才”培养计划(2012);2016年重庆医科大学优秀博士论文资助项目;2016年重庆市研究生科研创新项目。

Effects of estrogen replacement therapy on the myelin sheath of cerebral white matter and hippocampus and Lingo-1 expression in middle-aged ovariectomized rats

  • Received:2016-12-29 Revised:2017-04-26 Online:2017-07-05 Published:2017-06-23

摘要: 目的 检测经短期雌激素替代治疗(ERT)后中年卵巢切除大鼠大脑白质及海马内髓鞘相关指标及Lingo-1的表达,探讨雌激素对髓鞘作用的可能机制。方法 24只中年雌性SD大鼠行双侧卵巢切除术(OVX)后,随机分为安慰剂治疗组(OVX+Veh组)和雌激素替代治疗组(OVX+E组)。ERT 1个月后,Morris水迷宫检测大鼠空间学习和记忆能力。从各组大鼠随机选取10只,透射电子显微镜观察大脑白质及海马内髓鞘的超微结构;Western blot检测大脑白质及海马内髓磷脂碱性蛋白(MBP)及Lingo-1的含量;免疫组化方法检测 Lingo-1在大脑白质及海马的分布。结果 OVX+E组大鼠在定位航行实验中的潜伏期显著短于OVX+Veh组大鼠(P < 0.05); OVX+Veh组大鼠大脑白质和海马存在显著的髓鞘结构变性;OVX+E组大鼠大脑白质和海马中MBP的含量均显著高于OVX+Veh组(P < 0.05),而OVX+E组大鼠大脑白质和海马中Lingo-1的含量及分布均显著低于OVX+Veh组(P < 0.05)。结论 1个月的ERT对中年卵巢切除大鼠的认知功能及大脑白质和海马内的髓鞘具有明显的保护作用,这种保护作用可能与雌激素下调大脑白质和海马内Lingo-1的表达有关。

关键词: [关键词] 大脑白质, 海马, 中老年卵巢切除大鼠, 雌激素替代治疗, 髓鞘, Lingo-1。

Abstract: Objective To detect the expressions of Lingo-1 and myelin associated protein in the white matter and hippocampus of ovariectomized rats after short-term estrogen replacement therapy in order to explore the possible mechanisms for the effects of estrogen on the brain myelin sheaths and cognitive function. Methods 24 middle-aged (9-12 months) female Sprague-Dawley (SD) rats were bilaterally ovariectomized (OVX) and randomly divided into vehicle replacement (OVX+Veh) group and estrogen replacement (OVX+E) group. After one month ERT, The spatial learning and memory ability of all rats were assessed with Morris water maze. Then, 10 rats were randomly selected from each group. The ultrastucture of myelin sheaths in the cerebral white matter and hippocampus were observed using electron microscope transmission, and the protein expression levels of MBP and Lingo-1 were investigated with western blot and immunohistochemical staining. Results The escape latencies of OVX+E rats in navigation test were significantly shorter than that of OVX+Veh rats(P < 0.05). The myelin sheaths in the white matter and hippocampus of OVX+Veh rats showed obviously degeneration. In the OVX+E group, the expression of MBP in the white matter and hippocampus were significantly higher than that of OVX+Veh group(P < 0.05), however, the expression of Lingo-1 were significantly lower than that of OVX+Veh group(P < 0.05). Conclusions 1-month ERT had significant beneficial effects on the spatial learning capacity and myelin sheaths in the white matter and hippocampus. The protective effects may be related to estrogen-induced downregulation of the Lingo-1 expression in the white matter and hippocampus of rats.

Key words: [Key words]Cerebral white matter, Hippocampus, Middle-aged ovariectomized rats, Estrogen replacement therapy, Myelin sheath, Lingo-1

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