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

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（folliclestimulating 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。

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

Objective：To characterize 5-month-old ovariectomized and 18-month-old female rats as models for menopausal females.Methods：Sexual hormones FSH,LH and E2 were 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 ovariectomized 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 ovariectomized 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.