两种绝经状态大鼠模型性激素水平和下丘脑线粒体衰老的比较研究

神经药理学报 ›› 2011, Vol. 1 ›› Issue (2): 28-34.

两种绝经状态大鼠模型性激素水平和下丘脑线粒体衰老的比较研究

顾祖曦¹ ，徐莲薇²，孙卓君³，刘建文⁴，李盛男²，牟艳艳²，张焕英⁴，张婷婷²，桑珍³，马骏¹，陆雄¹

1. 上海中医药大学，上海，201203，中国 2. 上海中医药大学附属岳阳中西医结合医院，上海，200437，中国
3. 上海中医药大学附属曙光医院，上海，200021，中国

4. 上海华东理工大学药学院，上海，200237，中国

出版日期:2011-04-26 发布日期:2012-04-20
通讯作者: 徐莲薇，女，副主任医师，医学博士，硕士生导师；研究方向：中西医结合防治妇科疾病；E-mail：sherryxlw@hotmail.com
作者简介:顾祖曦，女，实验师；研究方向：医学实验动物学研究

Comparison of Sexual Hormone Levels and Hypothalamic Mitochondrial Aging in Two Rat Models of Menopausal Status

GU Zu-xi¹，XU Lian-wei²，SUN Zhuo-jun³，LIU Jian-wen⁴，LI Sheng-nan²，MOU Yan-yan⁴，ZHANG Huan-ying²，ZHANG Ting-ting²，SANG Zhen³，MA Jun¹，LU Xiong¹

1. Shanghai University of Traditional Chinese Medicine，Shanghai，201203，China
2. Shanghai Yueyang Integrated Traditional Chinese Medicine and Western Medicine Hospital，Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，200437，China

3. Shanghai Shuguang Hospital，Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，200021，China
4. Shanghai East China University of Technology，School of Pharmacy，Shanghai，200237，China

Online:2011-04-26 Published:2012-04-20

摘要/Abstract

摘要： 目的：通过观察去势 5 月龄 SD 雌性大鼠和 18 月龄 SD 雌性大鼠的性激素水平和下丘脑线粒体衰老变化，对两种绝经状态大鼠模型进行比较研究。方法：分别以去势 5 月龄和 18 月龄大鼠模拟绝经状态模型，以 5 月龄大鼠为青年对照组 24 月龄大鼠为老年对照组，比较两种大鼠模型与 5 月龄大鼠血清和下丘脑促卵泡成熟激素（follicle stimulating hormone,FSH ,促黄体生成素（luteinizing hormone LH ,雌二醇（estradiol E2），下丘脑超氧化物歧化酶（superoxide dismutase,SOD , 丙二醛（malondialdehyde,MDA）和总抗氧化能力（total anti-oxidative capacity,T-AOC）的变化，两种大鼠模型与 5 月龄 24 月龄大鼠下丘脑 mt-DNA 损伤基因 CoⅠ、CoⅢ表达和电镜下丘脑组织线粒体形态变化。结果：与 5 月龄大鼠相比，去势 5 月龄和 18 月龄大鼠血清和下丘脑 FSH、LH 水平均显著升高（P<0.05）， E2 水平均显著降低（P<0.05）；去势 5 月龄和 18 月龄大鼠下丘脑 SOD、T-AOC 水平均显著降低（P<0.01）。各组大鼠 ,下丘脑 mt-DNA 损伤基因 CoⅠ、CoⅢ表达差异显著，两种基因均呈现 5 月龄大鼠 < 去势 5 月龄大鼠 <18 月龄大鼠 <24 月龄大鼠的规律（P<0.001）。电镜下去势 5 月龄和 18 月龄大鼠下丘脑神经元细胞的线粒体呈明显损伤状态。结论：去势 5 月龄和 18 月龄两种大鼠模型均存在类似女性绝经后血清高 FSH、LH、低 E2 的内分泌表现；同时，去势 5 月龄大鼠切除卵巢 8 周以后，随着雌激素水平的急剧下降，生殖轴中枢下丘脑线粒体和 18 月龄大鼠同样存在衰老变化。因此，这两种大鼠模型均可以模拟女性绝经后生殖轴内分泌紊乱和下丘脑衰老的状态。

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关键词: 绝经, 大鼠模型, 下丘脑, mt-DNA损伤, 性激素, SOD, MDA, T-AOC

Abstract: Objective: To characterize 5-month-old ovariectomized and 18-month-old female rats as models for menopausal females. Methods: Sexual hormones FSH, LH and E₂were measured in serum and hypothalamus, and superoxide dismutase（SOD）, malondialdehyde（MDA）and total anti-oxidative capacity（T-AOC）in hypothalamus of a total of 71 Sprague Dawley female rats of 4 groups: 5-month-old control group, 5-month-old ovariectomized model group, 18-months-old model group and 24-month-old aged control group. Mitochondria DNA damage was monitored by measuring expression level of mRNA of CoⅠ and CoⅢ using quantitative RT-PCR. Ultrastructure of mitochondria of hypothalamus neuron cells was investigated using transmission electron microscope. Results: Compared with 5-month-old control rats, FSH and LH increased and E₂ decreased in serum and hypothalamus significantly（P<0.05）in both 5-month-old ovariectomized rats and 18-month-old rats. Antioxidants SOD and T-AOC of hypothalamus were reduced significantly in 5-month-old ova-riectomized rats and 18-month-old rats（P<0.01）. The expression levels of CoⅠ and Co Ⅲ, indications of hypothalamus mitochondria DNA damage, were at lowest in 5-month-old controls rats followed by ovariectomized 5-month-old rats, 18-month-old rats and 24-month-old rats（P<0.001）. Ultrastructural impairment of mitochondria of hypothalamic neuron cells was visible in both 5-month-old ovariecto-mized rats and 18-month-old rats. Conclusion: Both 5-month-old ovariectomied rats and 18-month-old rats have sexual hormones changes similar to that of menopausal females. Removal of bilateral ovaries in young rats not only lead to hormonal change but also results in mitochondria aging as 18-month-old rats have. Thus both 5-month-old ovariectomized rats and 18-month-old rats may mimic the status of sex endocrine change and hypothalamus aging in menopause females.

Key words:

menopause, rat model, hypothalamus, mt-DNA damage, sexual hormone, superoxide dismutase (SOD), malondialdehyde (MDA), total anti-oxidative capacity (T-AOC)

中图分类号:

R977.12

顾祖曦, 徐莲薇, 孙卓君, 刘建文, 李盛楠, 牟艳艳, 张焕英, 张婷婷, 桑珍, 马骏, 陆雄. 两种绝经状态大鼠模型性激素水平和下丘脑线粒体衰老的比较研究[J]. 神经药理学报, 2011, 1(2): 28-34.

GU Zu-xi, XU Lian-wei, SUN Zhuo-jun, LIU Jian-wen, LI Sheng-nan, MOU Yan-yan, ZHANG Huan-ying, ZHANG Ting-ting, SANG Zhen, MA Jun, LU Xiong. Comparison of Sexual Hormone Levels and Hypothalamic Mitochondrial Aging in Two Rat Models of Menopausal Status[J]. ACTA NEUROPHARMACOLOGICA, 2011, 1(2): 28-34.

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