淫羊藿苷预防给药对快速老化小鼠SAMP8学习记忆能力及脑组织线粒体氧化应激的影响

Effect of preventive administration of icariin on learning and memory abilities and brain mitochondrial oxidative stress in SAMP8

目的考察淫羊藿苷(icariin,ICA)预防给药对快速老化小鼠SAMP8学习记忆能力及脑组织线粒体氧化应激的影响。方法选择即将出现学习记忆障碍的6月龄快速老化小鼠SAMP8为实验对象,随机分为模型组、ICA组(75,150 mg·kg-1)、阳性药己烯雌酚组和雌激素受体抑制剂ICI182780联合ICA高剂量(150 mg·kg-1)组,以同月龄抗快速老化小鼠SAMR1为正常对照。预先灌胃给药8周,用Morris水迷宫和跳台行为学实验检测ICA预防给药对SAMP8小鼠学习记忆能力的影响。提取脑线粒体,通过测定脑组织线粒体内活性氧(ROS)水平、脂质过氧化物(MDA)含量、还原性谷胱甘肽GSH含量和过氧化氢酶(CAT)的活力,研究ICA预防给药对SAMP8小鼠脑组织线粒体氧化应激的影响。结果 ICA预防给药可以明显改善SAMP8小鼠的定位航行能力以及空间探索能力,提高其在跳台实验中的被动回避条件反射能力,减少SAMP8小鼠脑组织线粒体ROS水平和MDA含量,增加GSH含量,但对CAT活性作用不明显。ICA和ICI182780联合给药后,与ICA单独给药组相比,ICA对SAMP8小鼠学习记忆能力的改善作用明显降低,对脑组织线粒体氧化应激的改善作用变化不大。结论ICA预防给药可明显改善快速老化小鼠SAMP8学习记忆能力及脑组织线粒体氧化应激的水平,其改善学习记忆能力的作用机制可能与其植物雌激素样作用有关,其对脑组织线粒体发挥抗氧化应激的作用可能与雌激素受体无关。

Aim To investigate the effect of preventive administration of icariin on learning and memory abili-ties and brain mitochondrial oxidative stress in senes-cence-accelerated mouse prone8 ( SAMP8 ) . Methods <br> The 6-month-old SAMP8 mice were randomly divid-ed into the SAMP8 model group, ICA groups (75, 150 mg · kg-1 ) , the positive Diethylstilbestrol ( DES ) group and estrogen receptor inhibitor ICI182780 com-bined with ICA (150 mg·kg-1 ) group, with 8 mice in each group. 8 same month old SAMR1 mice were selected as the normal control group. After oral admin-istration for 8 weeks, Morris water maze test and step-down passive test were used to investigate the effects of preventive administration of ICA on learning and mem-ory abilities in SAMP8 mice. Cerebral cortex mitochon-dria were isolated to determine the effect of preventive administration of ICA on the oxidative stress by detec-ting reactive oxygen species ( ROS) level, lipid perox-ides ( MDA ) content, glutathione GSH content and catalase ( CAT ) activity. Results Preventive treat-ment of ICA could significantly improve the abilities of place navigation and space exploration of SAMP8 mice, enhance their reflex ability in step-down passive test. ICA could also reduce the level of ROS and MDA content, increase GSH content in brain mitochondria of SAMP8 mice. CAT activity was not obviously changed. Compared with ICA high dose group, the learning and memory abilities of mice in ICA and estrogen receptor inhibitor ICI182780 co-administrated group were signif-icantly decreased. However,brain mitochondria oxida-tive stress was not changed obviously. Conclusion Preventive administration of icariin can significantly improve learning and memory abilities and brain mito-chondrial oxidative stress in SAMP8 mice. The mecha-nism of ICA improving learning and memory abilities may be related to its estrogen-like effect;while the ac-tion on brain mitochondrial oxidative stress may be in-dependent of estrogen receptor.