雌激素替代治疗对中老年卵巢切除大鼠白质及白质内有髓神经纤维髓鞘超微结构作用的研究

Effect of estrogen replacement on the white matter and the myelin sheath ultrastructure of the myelinated fibers in the white matter of middle-aged ovariectomized rats

摘要:

目的：研究雌激素替代治疗（estrogen replacement therapy，ＥＲＴ）对中老年卵巢切除雌性SD大鼠大脑白质及白质内有髓神经纤维髓鞘超微结构的作用，为以后进一步运用ＥＲＴ疗延缓大脑衰老进程和防治脱髓鞘疾病提供科学依据。方法：选用40只10~12月龄中老年雌性SD大鼠行双侧卵巢切除术，术后1月将成功去势的19只卵巢切除大鼠按完全随机设计方式分为实验组（n=10）与对照组（n=9），前者给予17β-雌二醇颈背部皮下注射4周，后者给予安慰剂颈背部皮下注射4周。然后采用Morris水迷宫测试2组大鼠的空间参考记忆能力，运用电镜技术及相应的体视学方法对2组大鼠大脑白质及白质内有髓神经纤维髓鞘超微结构进行定量研究。结果：实验组大鼠与对照组相比，其空间参考记忆能力明显增强（F=9.645，P=0.006）。与对照组大鼠相比，实验组大鼠大脑白质内有髓神经纤维髓鞘总体积和髓鞘内外周长之差均明显增加[（32.94±5.97） mm3，（25.93±2.83） mm3，t=2.391，P=0.040；（1.16 ± 0.10） ?滋m、（1.03±0.09） ?滋m，t=2.325，P=0.045]。统计学相关分析发现，白质内有髓神经纤维髓鞘总体积与Morris水迷宫第1天潜伏期呈负相关（r=-0.744，P=0.009）。结论：ERT对中老年卵巢切除大鼠的空间参考记忆能力及白质内有髓神经纤维髓鞘均有积极的保护作用。

Abstract:

Objective：To investigate the effects of the short-term estrogen replacement therapy（ERT） on the white matter and the myelin sheath ultrastructure of the myelinated fibers in the white matter of ovariectomized middle-aged rats in order to provide a sci－entific basis for delaying the process of brain aging and combating demyelination diseases with estrogen replacement therapy in the future. Methods：Middle-aged female sprague-dawley rats of 10-12 month（40 rats） were bilaterally ovariectomized and the serum e－strogen levels were examined one month after the surgery. The female Sprague-Dawley rats（19 rats） with successful castration were ran－domly divided into experimental group（n=10） and control group（n=9）. Experimental rats were subcutaneously injected 17β-estradiol and control rats were subcutaneously injected placebo for 4 weeks. Then，the spatial reference memory capacities of two group rats were tested with Morris water maze. The white matter and the myeli－nated nerve fibers in the white matter of two group rats were quantitatively investigated with the transmission electron mi－croscope technique and the stereological techniques. Results：The spatial reference memory capacity of the experimental rats was significantly enhanced compared with that of the control rats（F=9.645，P=0.006）. The total volume of the myelin sheaths and the difference between outer perimeter and inner perimeter of myelin sheaths in the myelinated fibers of the white matter in experimental rats were significantly increased compared with those of control rats（（32.94±5.97） mm3，（25.93±2.83） mm3，t=2.391，P=0.040；（1.16±0.10） ?滋m，（1.03±0.09） ?滋m，t=2.325，P=0.045）. The correlation analyses suggested that the total myelin sheath vol－ume of the myelinated fibers in the white matter was significantly and negatively correlated with the escape latency on the first day of Morris water maze（r=-0.744，P=0.009）. Conclusions：Estrogen replacement had positive protective effects on the spatial reference memory capacity and the myelin sheaths of the myelinated fibers in the white matter of the middle-aged ovariectomized rats.