芎归不忘散对脑缺血大鼠学习记忆障碍及其线粒体、PI3K/Akt信号通路作用机制研究  

Mechanism of Xionggui Buwang San Protecting Mitochondrial Function against Vascular Dementia through PI3K/AKT Signal Pathway

作　　者：付颖 文雯[1,2] 魏江平 陈欢[1,2] 文跃强 徐世军[1,2] Fu Ying;Wen Wen;Wei Jiangping;Chen Huan;Wen Yueqiang;Xu Shijun(School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu,Sichuan 611137;Institute of Meterial Medica Integration and Transformation for Brain Disorders,CDUTCM,Sichuan 611137;School of Basic Medicine,Chengdu University of Traditional Chinese Medicine,Chengdu,Sichuan 611137)

机构地区：[1]成都中医药大学药学院,成都611137 [2]成都中医药大学中医脑病药物整合转化研究所,成都611137 [3]成都中医药大学基础医学院,成都611137

出　　处：《世界科学技术-中医药现代化》2020年第6期1842-1848,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：四川省教育厅重点项目(17ZA0149):基于氨基酸类神经递质代谢研究芎归不忘散抗血管性痴呆的“解毒通络醒脑”作用及其机制,负责人:文跃强;四川省中医药管理局重点项目(2018JC013):基于IL-6/JAK2/STAT3信号通路探讨芎归不忘散对VD大鼠益智作用的分子机制,负责人:文跃强;成都中医药大学科学技术发展基金重点项目(ZRQN1611):基于脑能量代谢研究芎归不忘散抗血管性痴呆的“通络醒脑”作用及其机制,负责人:文跃强。

摘　　要：目的探讨芎归不忘散对血管性痴呆(vascular dementia,VD)模型大鼠线粒体保护及对PI3K/AKT信号通路的影响,揭示其抗血管性痴呆的作用机制。方法采用微血栓栓塞法制备VD大鼠模型;采用Morris水迷宫评价其学习记忆能力;HE染色法观察海马CA1区病理学形态学;流式细胞术检测大鼠海马线粒体肿胀及膜电位;HPLC测定脑组织ATP、ADP以及AMP的含量;Western Blot测定脑组织PI3K/AKT信号通路相关蛋白的表达。结果与模型组比较,芎归不忘散显著缩短模型大鼠逃避潜伏期(P<0.05),明显增加穿越平台次数(P<0.05),海马CA1区病理损害明显减轻;芎归不忘散高剂量组海马线粒体肿胀度明显减轻(P<0.05);高、低剂量组海马线粒膜电位显著增高(P<0.05),海马能荷值显著增高(P<0.05),p-PI3K、p-AKT表达显著增强。结论芎归不忘散能改善血管性痴呆学习记忆功能,激活PI3K/AKT信号通路保护线粒体功能是其主要作用机制之一。Objective To investigate the effect of XiongguiBuWangSan(XGBWS)on mitochondrial protection and PI3 K/AKT signaling pathway in vascular dementia(VD)model rats,and to reveal its anti-vascular dementia mechanism.METHODS VD rat model was established by microthromboembolism.To evaluate learning and memory ability Morris water maze was used,and to observe the pathomorphology of hippocampal CA1 region HE staining was used,flow cytometry was used to detect the swelling of hippocampal mitochondria and membrane potential,the content of ATP,ADP and AMP in hippocampus was determined by HPLC,Western Blot was used to detect the expression of PI3 K/AKT signaling pathway-related proteins in hippocampus.Result Compared with the model group,XGBWS could significantly shorten the escape latency(P<0.05),significantly increase the times of traversing the platform(P<0.05),significantly reduce the pathological damage of hippocampal CA1 area,and significantly reduce the swelling of hippocampal mitochondria in the high dose group(P<0.05).The expression of p-PI3 K and p-AKT in hippocampus and hippocampus increased significantly(P<0.05).Conclusion XGBWS can improve the learning and memory function of vascular dementia.Activating PI3 K/AKT signaling pathway to protect mitochondrial function may is one of its main mechanisms.

关 键 词：血管性痴呆 芎归不忘散 学习记忆功能 线粒体 PI3K/AKT信号通路 

分 类 号：R33[医药卫生—人体生理学]