红景天苷调控PI3K/Akt信号通路对永久性脑缺血大鼠的保护作用  

The therapeutic effect of salidroside on rats with permanent cerebral ischemia through regulating PI3K/Akt signaling pathway

作　　者：黄嘉慧 赵春蕊 聂婧雯 罗锐 黄私迎 孙春晓 杨泽霖 应雄[1] 洪桂祝 赖文芳[1] HUANG Jia-hui;ZHAO Chun-rui;NIE Jing-wen;LUO Rui;HUANG Si-ying;SUN Chun-xiao;YANG Ze-lin;YING Xiong;HONG Gui-zhu;LAI Wen-fang(College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建中医药大学药学院,福建福州350122

出　　处：《中国药理学通报》2021年第5期698-703,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81973503,81603323);福建省自然科学基金项目(No 2020J01727,2019J01345);福建省卫健委中青年骨干人才培养项目(No 2019-ZQN-74);福建省教育厅杰青项目,福建中医药大学资助项目(No X2018002-协同)。

摘　　要：目的研究红景天苷(salidroside,Sal)通过调控PI3K/AKT信号通路对永久性大脑中动脉闭塞模型(pMCAO)大鼠的神经保护作用及其机制。方法健康成年雄性SPF级雄性SD大鼠70只,其中30只大鼠随机分为假手术组(sham组)、模型组(pMCAO组)、红景天苷给药组(pMCAO+Sal组),线栓法造模成功后,对sham组和pMCAO组大鼠腹腔注射生理盐水,pMCAO+Sal组按照50 mg·kg^(-1)·d^(-1)腹腔注射红景天苷(50 mg·kg^(-1)·d^(-1)),给药1 d。40只大鼠随机分为假手术组(sham组)、模型组(pMCAO组)、红景天苷给药组(pMCAO+Sal组)、抑制剂组(pMCAO+Sal+LY组);侧脑室注射PI3K抑制剂30 min后,制备pMCAO模型,1 h后腹腔注射红景天苷,给药1 d。免疫组织化学染色测定脑组织中NeuN表达,Western blot分析脑组织中NeuN蛋白、NF-κBp50核蛋白的表达,RT-qPCR检测IL-6和TNF-α的表达。结果与pMCAO组比较,红景天苷作用后,NeuN免疫荧光染色表达量明显增加,且能够促进NeuN蛋白,抑制NF-κB p50核蛋白及IL-6和TNF-αmRNA表达。经PI3K抑制剂LY294002作用后,红景天苷对上述指标作用不明显。结论红景天苷能够通过调控PI3K/AKT信号通路,抑制NF-κB p50核转录水平,进而抑制炎症因子,对pMCAO模型大鼠具有神经保护的作用。Aim To investigate the neuroprotective effect and mechanism of salidroside(Sal)on rats with permanent middle cerebral artery occlusion model(pMCAO)by regulating the PI3K/AKT signaling pathway.Methods A total of 80 healthy adult SPF male SD rats were randomly divided into sham operation group(sham group),model group(pMCAO group),drug administration group(pMCAO+Sal group)and inhibitor group(pMCAO+Sal+YL group).After the pMCAO model rats were prepared by the line bolt method,salidroside(50 mg·kg^(-1)·d^(-1))was intraperitoneally injected and administered continuously for one day.Immunohistochemical staining was used to determine the expression of NeuN in brain tissue,Western blot was used to analyse NeuN protein,NF-κBp50 nuclear protein,and RT-qPCR was employed to detect IL-6 and TNF-αexpression.Results Compared with model group,the NeuN immunofluorescence staining expression significantly increased after salidroside was given,and NeuN protein was promoted and NF-κB p50 nuclear protein was inhibited,while salidroside inhibited the expression of inflammatory cytokines IL-6 and TNF-α.After the action of PI3K inhibitor LY294002,salidroside had no obvious effect on the above indexes.Conclusions Salidroside can inhibit NF-κB p50 nuclear transcription by regulating the PI3K/AKT signaling pathway,thereby inhibiting inflammatory factors,and has a neuroprotective effect on pMCAO model rats.

关 键 词：红景天苷 pMCAO 神经保护 PI3K/AKT信号通路 NEUN NF-κB p50 

分 类 号：R-332[医药卫生] R284.1