淫羊藿苷对快速老化小鼠SAMP8脑线粒体的保护作用  

Protective effects of icariin on cerebral mitochondria function in SAMP8 mice

作　　者：吴满刚[1] 贺晓丽[2] 强桂芬[3] 时丽丽[3] 李晓秀[3] 祖勉[3] 刘东华[1] 毕明刚[2] 杜冠华[3] 

机构地区：[1]哈尔滨商业大学生命科学与环境科学研究中心 [2]中国医学科学院药用植物研究所药理毒理研究中心,北京100193 [3]中国医学科学院药物研究所国家药物筛选中心,北京100050

出　　处：《中国临床药理学与治疗学》2010年第7期721-726,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金："重大新药创制"科技重大专项(2009ZX09301-003-11-2);国家自然科学基金项目(30772750)

摘　　要：目的:探讨淫羊藿苷(ICA)对快速老化小鼠SAMP8脑线粒体功能的影响。方法:将8月龄快速老化小鼠SAMP8随机分为模型组、盐酸多奈哌齐1mg/kg组、吡啦西坦200mg/kg组、ICA75mg/kg组和150mg/kg组,每组6只;8只同月龄抗快速老化小鼠SAMR1作为正常对照组。给药30d后,提取小鼠脑线粒体,测定线粒体呼吸功能、肿胀度、膜电位、活性氧(ROS)和ATP含量。结果:与SAMR1正常对照组相比,SAMP8小鼠脑线粒体呼吸功能显著降低,表现为线粒体Ⅲ态呼吸明显降低,Ⅳ态呼吸改变不明显,呼吸控制指数和磷氧比值降低(P<0.05);线粒体膜肿胀度增高,膜电位降低,线粒体内ROS含量增高,而ATP含量明显降低(P<0.05)。与SAMP8模型组相比,ICA75mg/kg和150mg/kg均可明显改善SAMP8小鼠脑线粒体结构和呼吸功能(P<0.05,P<0.01)。结论:ICA可明显改善SAMP8小鼠脑线粒体结构和功能。AIM：To investigate the protective effects of icariin （ICA） on cerebral mitochondria in senescence accelerated mice （SAM）. METHODS： The 8-month-old senescence-accelerated mouse prone /8（SAMP8） mice were divided into SAMP8 group, Donepezil Hydrochloride （DON）-treated SAMP8 group （1 mg/kg）, Piracetam （PIR）-treated SAMP8 group （200 mg/kg） and ICA-treated SAMP8 groups （75 mg/kg and 150 mg/kg）. The age-matched senescence-accelerated mouse resistance 1（ SAMR1） mice served as control. After treatment for 30 d, the cerebral mitochondria were isolated. The ATP production, reactive oxygen species （ROS） level, oxidative phosphorylation parameters and mitochondrial permeability transition pore （MPTP） were detected to evaluate the function of mitochondria in SAM mice. RESULTS：Respiratory control index, ADP/O ratio, State Ⅲ respiration and oxidative phosphorylation rate （OPR） were significantly lower in SAMP8 than those in SAMR1（P0.05）. State Ⅳ respiration did not significantly change in SAMP8 compared with that in SAMR1. At the same time, the loss of mitochondrial membrane potential（MMP）, the decreased of ATP content, the increase of mitochondrial swelling degree and the increased level of ROS were also observed in SAMP8 brain mitochondria. ICA at the dosage of 75 mg/kg and 150 mg/kg significantly improved oxidative phosphorylation process, mitochondria swelling degree, MMP and other biochemical functions. CONCLUSION： ICA has a protective effect on cerebral mitochondrial impairment in SAMP8 mice.

关 键 词：淫羊藿苷 快速老化小鼠 阿尔茨海默病 线粒体 

分 类 号：R965.2[医药卫生—药理学]