益肺宣肺降浊方通过EGFR调节PI3K/Akt-MAPK/Erk通路改善血管性痴呆大鼠的记忆  

Yifei Xuanfei Jiangzhuo Prescription(益肺宣肺降浊方)Improves Memory of Vascular Dementia Rats by EGFR Regulating PI3K/Akt-MAPK/Erk Pathway

作　　者：陈炜 朱小敏[3] 胡跃强 洪煌钟[3] 蒋宇龙 宾新铭 江家乔 肖钰雯 吴林 CHEN Wei;ZHU Xiaomin;HU Yueqiang;HONG Huangzhong;JIANG Yulong;BIN Xinming;JIANG Jiaqjiao;XIAO Yuwen;WU Lin(Graduate School of Jiangxi University of Chinese Medicine,Nanchang 330004,Jiangxi,China;The First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,Guangxi,China;Graduate School of Guangxi University of Chinese Medicine,Nanning 530001,Guangxi,China;Scientific Experiment Center,Guangxi University of Chinese Medicine,Nanning 530001,Guangxi,China)

机构地区：[1]江西中医药大学研究生院,江西南昌330004 [2]广西中医药大学第一附属医院,广西南宁530023 [3]广西中医药大学研究生院,广西南宁530001 [4]广西中医药大学科学实验中心,广西南宁530001

出　　处：《中华中医药学刊》2023年第8期46-50,I0018-I0021,共9页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金地区科学基金项目(81760847);广西高等学校高水平创新团队及卓越学者计划项目(桂教人才[2020]6号);广西中医药重点学科建设项目(GZXK-Z-20-13);广西中医脑病临床研究中心项目(桂科AD20238028);广西中医药大学第一附属医院学术团队建设项目(院字[2018]146号)。

摘　　要：目的 探讨益肺宣肺降浊方通过表皮生长因子受体(Objective Epidermal growth factor receptor, EGFR)调节PI3K/Akt-MAPK/Erk通路改善对血管性痴呆(VaD)的作用及机制。方法 建立大脑中动脉栓塞法(Middle Cerebral Artery Occlusion, MCAO)大鼠血管性痴呆模型;给予益肺宣肺降浊方联合PTEN、EGFR和MAPK抑制剂,进行行为学实验,并运用Western Blot、免疫荧光、电镜透射等技术检测益肺宣肺降浊方对VaD可能通过PI3K/Akt和MAPK/Erk信号通路作用机制进行探索。结果 益肺宣肺降浊方呈剂量依赖性改善VaD大鼠的记忆能力及脑海马组织的病理、降低神经元凋亡。上调EGFR激活PI3K/Akt信号通路与MAPK/Erk信号通活性。结论 益肺宣肺降浊方对VaD大鼠的作用可能通过VEGF受体EGFR调节PI3K/Akt信号通路与MAPK/Erk信号通活性,以及PI3K/Akt与raf1-MAPK/Erk的串扰作用,增强Erk1/2磷酸化,进而促进神经细胞存活、神经元形态,最终达到修复记忆能力,治疗血管性痴呆的作用。Objective Vascular dementia(VaD)is a common clinical disease,which seriously endangers human health.The purpose of this study was to investigate the effect and mechanism of Yifei Xuanfei Jiangzhuo Prescription(益肺宣肺降浊方)on VaD.Methods The vascular dementia model of MCAO rats was established.Yifei Xuanfei Jiangzhuo Prescription combined with PTEN,epidermal growth factor receptor(EGFR)and mitogen-activated protein kinase(MAPK)inhibitors were given for behavioral experiment.Western Blot,immunofluorescence,transmission electron microscopy and other techniques were used to detect the possible mechanism of Yifei Xuanfei Jiangzhuo Prescription treating VaD through phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)and MAPK/extracellular regulated protein kinases(Erk)signaling pathways.Results The results showed that Yifei Xuanfei Jiangzhuo Prescription could improve the memory ability and pathological changes of hippocampal tissue in brain and reduce the neuronal apoptosis in VaD rats in a dose-dependent manner.It can up-regulated the activities of EGFR-activated PI3K/Akt signaling pathway and MAPK/Erk signaling.Conclusion The effect of Yifei Xuanfei Jiangzhuo Prescription on VaD rats may be through the regulation of PI3K/Akt signaling pathway and MAPK/Erk signaling activity by VEGF receptor EGFR as well as crosstalk effect between PI3K/Akt and raf1-MAPK/Erk to enhance Erk1/2 phosphorylation,thereby promoting the survival of nerve cells,neuronal morphology,and eventually achieving the effect of repairing of memory ability and treating of vascular dementia.

关 键 词：益肺宣肺降浊方 血管性痴呆 EGFR PI3K/AKT raf1-MAPK/Erk 

分 类 号：R285.5[医药卫生—中药学]