摘要
目的：探讨地黄饮子对阿尔茨海默病（AD）大鼠中枢神经线粒体生物合成能力、氧化损伤保护的作用机制以及对AD大鼠学习记忆能力的改善作用。方法：120只雄性SD大鼠,随机分为假手术组、模型组、安理申组、地黄饮子高、中、低剂量组,除假手术组外均侧脑室注射β-淀粉样蛋白1-42（Aβ1-42）建立AD模型,各治疗组给予相应药物灌胃,假手术组和模型组大鼠给予等体积生理盐水灌胃,每天1次,连续30 d。通过大鼠避暗箱实验,Y迷宫实验对大鼠行为学进行观察。行为学实验后,蛋白免疫印迹法（Western blot）检测过氧化物酶体增生物激活受体γ共激活因子1α（PGC-1α）表达量和环磷腺苷效应元件结合蛋白（CREB）磷酸化水平;测定脑组织线粒体呼吸链复合物Ⅰ,Ⅱ,Ⅲ和Ⅳ活性;测定丙二醛（MDA）水平及超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）活性。结果：地黄饮子可显著改善AD大鼠学习记忆和工作记忆能力。与模型组比较,在避暗箱实验中,地黄饮子可使AD大鼠的停留潜伏期明显增加（P〈0.05,P〈0.01）,而错误次数显著减少（P〈0.05,P〈0.01）;Y迷宫实验中,地黄饮子可显著提高AD大鼠自发交替反应率（P〈0.05,P〈0.01）。地黄饮子显著增加AD大鼠脑组织PGC-1α表达量和CREB磷酸化水平,显著提高脑组织线粒体呼吸链复合物Ⅰ,Ⅲ和Ⅳ活性（P〈0.01）,而对呼吸链复合物Ⅱ活性无显著作用。地黄饮子能显著降低AD大鼠脑组织MDA含量（P〈0.01）,提高抗氧化酶类SOD和GSH-Px活性（P〈0.05,P〈0.01）。结论：地黄饮子通过激活AD大鼠CREB/PGC-1α信号通路,提高线粒体生物合成能力,增加线粒体呼吸链酶系活性,改善线粒体功能损伤,同时通过增强抗氧化酶系活性,发挥提高机体抗氧化损伤,从而改善AD大鼠学习记忆和工作记忆能力。
Objective： To investigate the effects of Dihuang Yinzi on mitochondrial biosynthesis,oxidative stress as well as learning and memory ability in Alzheimer＇s disease（ AD） rats. Method： Totally 120 male rats were randomly distributed into sham operation group,AD model group,Aricept group,high-,moderate and low-dosage Dihuang Yinzi groups. Animals in all groups except the sham operation group were injected withβ-amyloid protein 1-42（ Aβ1-42） via lateral ventricles to establish AD model. Corresponding drug were given via intragastric administration,while those in sham operation group and AD model group were administrated with the same volume of normal saline. The administrations were performed once a day and were consecutively carried out for 30 days. The behavior of rats was assessed with avoiding dark test and Y-maze test,respectively. After behavioral tests,the expression of c AMP responsive element-binding protein（ CREB） and peroxisome proliferatoractivated receptor γ coactivator-1α（ PGC-lα） were determined by Western blot. Activities of respiratory chain complex I,Ⅱ,Ⅲ,and Ⅳ,the level of malondialdehyde（ MDA）,and activities of superoxide dismutase（ SOD）and glutathione peroxidase（ GSH-Px） in mitochondria of brain tissues were detected respectively. Result： Dihuang Yinzi can significantly improve the learning memory ability and working memory ability of AD rats. In comparison with AD model group,Dihuang Yinzi treatment could increase the stay-latency and decrease the error times of AD rats in avoiding dark test（ P 〈 0. 05,P 〈 0. 01）. The spontaneous alternation in AD rats was significantly increased by Dihuang Yinzi in Y-maze test（ P 〈 0. 05,P 〈 0. 01）. Dihuang Yinzi could significantly up-regulate the phosphorylation of cyclic adenosine monophosphae and the expression of PGC-lα and significantly increase the activity of respiratory chain complex Ⅰ,Ⅲ and Ⅳ in AD rats（ P 〈 0. 01）,but had no obvious effect on the activity of complex Ⅱ Dihuang Yinzi could also reduce the level of cerebral MDA（ P 〈 0. 01） and improve the activities of SOD and GSH-Px（ P 〈 0. 05,P 〈 0. 01）. Conclusion： Dihuang Yinzi can improve the cognition of AD rats significantly via activating the CREB/PGC-1α pathway,increase the mitochondrial biosynthesis and mitochondrial respiratory chain enzyme activity,improve mitochondrial dysfunction,and improve the body＇s ability against oxidative damages,thereby improving learning memory ability and working memory ability in AD rats by enhancing antioxidant enzyme activity.
作者
闫妍
韩冉
高俊峰
唐旭
张娜
马涛
YAN Yan;HAN Ran;GAO Jun-feng;TANG Xu;ZHANG Na;MA Tao(Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2018年第21期105-110,共6页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81673929)
