Shi Chun, Xu Jie
Department of Anatomy, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
J Bioenerg Biomembr. 2008 Dec;40(6):625-30. doi: 10.1007/s10863-008-9195-1. Epub 2009 Jan 13.
In the present study, to determine whether aging could increase the vulnerability of the brain to estrogen withdrawal-induced mitochondrial dysfunction, we measured the cytochrome c oxidase (COX) activity and mitochondrial adenosine triphosphate (ATP) content in hippocampi of 2 groups of ovariectomized (OVX) Wistar rats aged 2 months (young) and 9 months (middle-aged), respectively. In addition, effects of genistein and estradiol benzoate (EB) were tested also. We observed only a transient alteration of COX activity and mitochondrial ATP content in hippocampi of young OVX rats but a prolonged lowering of COX activity and mitochondrial ATP content in hippocampi of middle-aged OVX rats. This suggested that with aging compensatory mechanisms of mitochondrial function were attenuated, thus exacerbated estrogen withdrawal-induced mitochondrial dysfunction in hippocampi. Significantly, EB/genistein treatment reversed this estrogen withdrawal-induced mitochondrial dysfunction in both young and middle-aged rats suggesting that genistein may be used as a substitute for estradiol to prevent age-related disease such as Alzheimer's disease in post-menopausal females.
在本研究中，为了确定衰老是否会增加大脑对雌激素撤药诱导的线粒体功能障碍的易感性，我们分别测量了两组卵巢切除（OVX）的Wistar大鼠海马体中的细胞色素c氧化酶（COX）活性和线粒体三磷酸腺苷（ATP）含量，这两组大鼠的年龄分别为2个月（年轻）和9个月（中年）。此外，还测试了染料木黄酮和苯甲酸雌二醇（EB）的作用。我们观察到，年轻OVX大鼠海马体中的COX活性和线粒体ATP含量仅出现短暂变化，而中年OVX大鼠海马体中的COX活性和线粒体ATP含量则出现长期降低。这表明随着衰老，线粒体功能的代偿机制减弱，从而加剧了雌激素撤药诱导的海马体线粒体功能障碍。值得注意的是，EB/染料木黄酮治疗可逆转年轻和中年大鼠中这种雌激素撤药诱导的线粒体功能障碍，这表明染料木黄酮可用作雌二醇的替代品，以预防绝经后女性的年龄相关疾病，如阿尔茨海默病。
