本文選題：雌激素替代治療　切入點：髓鞘　出處：《重慶醫(yī)科大學》2014年碩士論文

【摘要】：已有大量研究表明，雌激素可直接作用于中樞神經(jīng)系統(tǒng)，對學習、記憶、情感等功能有重要影響。流行病學結果顯示，，絕經(jīng)后女性罹患阿爾茨海默�。ˋlzheimer's disease,AD）的風險明顯高于男性；且在圍絕經(jīng)期使用雌激素治療可以延緩AD的發(fā)生，提高老年大腦的認知能力。我們選用中老年雌性大鼠行雙側卵巢切除術（ovariectomy，OVX），將成功去勢的大鼠隨機分為兩組，雌激素替代治療組（OVX+E組）給予17-β雌二醇皮下注射，安慰劑對照組（OVX+O組）給予安慰劑皮下注射。運用Morris水迷宮測試大鼠空間記憶能力；并運用透射電子顯微鏡和新的體視學方法研究大鼠海馬CA1區(qū)有髓神經(jīng)纖維髓鞘的改變。 第一部分 1.材料與方法 1.119只雌性SD大鼠（10～12月齡）行雙側卵巢切除術，術后連續(xù)陰道涂片及測定循環(huán)雌激素濃度篩選成功去勢大鼠，隨機分為OVX+E組（10只）和OVX+O組（9只）。 1.2OVX+E組給予連續(xù)4周17-β雌二醇皮下注射，OVX+O組給予連續(xù)4周安慰劑皮下注射。最后一天注射后測定大鼠循環(huán)雌激素濃度，分離取出子宮進行稱重。 1.3運用Morris水迷宮測試兩組大鼠的空間記憶能力。 2.結果 2.1OVX+O大鼠體內(nèi)循環(huán)雌激素水平顯著低于OVX+E組大鼠（P0.05）, OVX組大鼠的子宮較OVX+E組大鼠顯著萎縮（P0.05）。 2.2OVX+E組大鼠Morris水迷宮的平均潛伏期較OVX+O組大鼠顯著性縮短（P0.05）。 第二部分 1.材料與方法 1.1從OVX+E組隨機挑選6只、OVX+O組隨機挑選5只大鼠大腦半球制作1mm連續(xù)切片，并用解剖顯微鏡拍照。 1.2在連續(xù)腦片上隨機抽取5～7塊包含海馬CA1的組織塊制成超薄切片，每張切片隨機抽取5～10個視野在透射電子顯微鏡下放大20000倍拍照，每只動物共拍攝50張照片。 1.3運用體視學方法計算海馬CA1體積、CA1有髓神經(jīng)纖維及其髓鞘體積。 1.4測量海馬CA1內(nèi)有髓神經(jīng)纖維直徑、有髓神經(jīng)纖維軸突直徑及有髓神經(jīng)纖維髓鞘厚度。 2.結果 2.1OVX+O組海馬CA1體積為26.83±1.17mm3，OVX+E組大鼠海馬CA1體積為27.85±1.15mm3，兩組之間無顯著性差異（P0.05）。兩組大鼠的有髓神經(jīng)纖維體積不存在顯著性差異（P0.05）。兩組大鼠的有髓神經(jīng)纖維髓鞘體積也沒有顯著性差異（P0.05）。 2.2OVX+E組大鼠海馬CA1有髓神經(jīng)纖維平均直徑與OVX+O組的比較無顯著性差異（P0.05），兩組大鼠有髓神經(jīng)纖維軸突平均直徑的比較亦不具有顯著性差異（P0.05）。 2.3OVX+E組大鼠直徑為0.6~0.7μm的有髓神經(jīng)纖維髓鞘厚度比OVX+O組大鼠顯著性增加14.1%（P0.05）。OVX+E組大鼠直徑為0.8~0.9μm的有髓神經(jīng)纖維直徑與軸突直徑差較OVX+O組大鼠顯著性增加18.2%（P0.05）。 全文結論 1.連續(xù)4周雌激素替代治療可以改善中老年大鼠的空間參考記憶能力。 2.雌激素替代治療對中老年大鼠海馬CA1體積沒有顯著性影響。 3.獲得了雌激素缺乏及雌激素替代治療的中老年大鼠海馬CA1內(nèi)有髓神經(jīng)纖維體積、髓鞘體積、髓鞘厚度的參數(shù)，為以后研究雌激素替代治療延緩大腦衰老、治療神經(jīng)退行性疾病等提供了重要的科學依據(jù)。 4.雌激素替代治療可以防止海馬內(nèi)有髓神經(jīng)纖維髓鞘丟失和/或促進髓鞘形成增加，其中以中等直徑的有髓神經(jīng)纖維髓鞘改變?yōu)橹鳌?br/>[Abstract]:A large number of studies have indicated that estrogen can act directly on the central nervous system, learning, memory, emotion has an important influence function. Epidemiological results show that postmenopausal women suffering from Alzheimer's disease (Alzheimer's, disease, AD) the risk is significantly higher than male; and in perimenopausal estrogen therapy can delay the occurrence of AD, improve cognitive ability the old brain. We use in aged female rats underwent bilateral ovariectomy (ovariectomy, OVX), the rats were randomly divided into two groups successfully ovariectomized, estrogen replacement therapy group (OVX+E group) received 17- subcutaneous injection of estradiol, placebo control group (group OVX+O) received placebo subcutaneously by Morris water maze. To test the spatial memory of rats; and by transmission electron microscopy and stereological methods in rat hippocampal CA1 area of myelinated nerve fiber myelin changes.
Part one
1. materials and methods
1.119 female SD rats (10~12 months old) underwent bilateral ovariectomy, and determination of circulating estrogen concentration in ovariectomized rats successfully screened continuous vaginal smear after surgery, were randomly divided into OVX+E group (10 rats) and OVX+O group (9).
Group 1.2OVX+E was given subcutaneous injection of 17- beta estradiol for 4 weeks. OVX+O group was given subcutaneous injection of placebo for 4 weeks. After the last day, the concentration of circulating estrogen was measured, and the uterus was removed and weighed.
1.3 the Morris water maze was used to test the spatial memory ability of the two groups of rats.
2. results
The level of circulating estrogen in 2.1OVX+O rats was significantly lower than that in group OVX+E (P0.05), and the uterus of group OVX rats was significantly atrophied than that in group OVX+E (P0.05).
The average latency of Morris water maze in group 2.2OVX+E rats was significantly shorter than that in group OVX+O (P0.05).
The second part
1. materials and methods
1.1 from group OVX+E, 6 were selected randomly. Group OVX+O randomly selected 5 rat cerebral hemispheres to make 1mm continuous slices and photographed with an anatomical microscope.
1.2 randomly selected 5~7 blocks containing hippocampal CA1 from the continuous brain slices to make ultrathin slices. 5~10 slices were randomly selected from each slice, and 20000 times were taken up under transmission electron microscope. 50 photos were taken by each animal.
1.3 the volume of hippocampal CA1 was calculated by stereological method, and myelinated nerve fiber and its myelin sheath volume were found in CA1.
1.4 the diameter of the myelinated nerve fibers in the hippocampal CA1, the diameter of the myelinated nerve fiber axons and the myelin sheath thickness of the myelinated nerve fibers were measured.
2. results
In group 2.1OVX+O, the volume of CA1 was 26.83 + 1.17mm3, OVX+E group CA1 of the rat hippocampus volume was 27.85 + 1.15mm3, there was no significant difference between the two groups (P0.05). The two groups of rats of myelinated nerve fiber volume had no significant difference (P0.05). The two groups of rats of myelin volume there were no significant differences (P0.05).
The mean diameter of CA1 myelinated nerve fibers in hippocampus of 2.2OVX+E group was not significantly different from that of OVX+O group (P0.05). There was no significant difference in mean diameter of myelinated nerve axons between two groups (P0.05).
In group 2.3OVX+E, myelin sheath thickness of myelinated nerve fibers with diameter of 0.6~0.7 mu m in group A was significantly increased by 14.1% (P0.05) than that in group OVX+O, and the diameter and diameter of myelinated nerve fibers in 0.8~0.9 group were significantly increased by 18.2% (P0.05) than those in OVX+O group.
Full text conclusion
1. consecutive 4 weeks of estrogen replacement therapy can improve the spatial reference memory ability of middle and old aged rats.
2. estrogen replacement therapy had no significant effect on the volume of CA1 in the hippocampus of middle aged and old rats.
3. the lack of estrogen and estrogen replacement therapy of CA1 in hippocampus in aged rats myelinated nerve fibers in the volume, volume of myelin, myelin sheath thickness parameters, for the study of estrogen replacement therapy to slow brain aging, treatment of neurodegenerative diseases provides an important scientific basis.
4. estrogen replacement therapy can prevent myelin sheath loss and / or myelin formation in the hippocampus, and myelin sheath changes in medium diameter myelinated nerve fibers.

【學位授予單位】：重慶醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R713.6

【參考文獻】

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本文編號：1705957