黄芪总苷调节蛋白激酶B-叉头框蛋白O1/3信号通路对大鼠脑缺血模型脑水肿的治疗作用研究  

Therapeutic Effect of Total Astragalus Saponins on Cerebral Edema in Ischemic Model Rats by Regulating Protein Kinase B-forkhead Box Protein O 1/3 Pathway

作　　者：余仕猛 雷超[2] 李侃 谭倩 从林 马荣芳[1] 柳青 YU Shi-meng;LEI Chao;LI Kan;TAN Qian;CONG Lin;MA Rong-fang;LIU Qing(Department of Neurology,the Affiliated Hospital of Xinyang Vocational and Technical College,Xinyang 464000,China;Department of Geriatrics,Liyuan Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430077,China;Department of Neurology,Dawu County People’s Hospital,Xiaogan 432800,China;Department of Endocrinology,Liyuan Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430077,China;Department of Neurology,Xinyang Central Hospital,Xinyang 464000,China;Department of Neurology,Shaoxing Traditional Chinese Medicaine Hospital,Shaoxing 312099,China)

机构地区：[1]信阳职业技术学院附属医院神经内科,信阳464000 [2]老华中科技大学同济医学院附属梨园医院老年科,武汉430077 [3]大悟县人民医院神经内科,孝感432800 [4]华中科技大学同济医学院附属梨园医院内分泌科,武汉430077 [5]信阳市中心医院神经内科,信阳464000 [6]绍兴市中医院神经内科,绍兴312099

出　　处：《中国临床神经科学》2024年第6期620-628,共9页Chinese Journal of Clinical Neurosciences

基　　金：河南省医学科技攻关计划项目(编号:LHGJ20221060)。

摘　　要：目的探究黄芪总苷(AST)调节蛋白激酶B(AKT)-叉头框蛋白O(FOXO)1/3信号通路对大鼠脑缺血模型脑水肿的治疗作用。方法取SD大鼠采用线栓法制作大脑中动脉栓塞(MCAO)模型,随机分为模型组、AST低剂量(AST-L 56 mg·kg^(-1))组、AST高剂量(AST-H 112 mg·kg^(-1))组、AST-H+MK-2206组和假手术组(均n=10)。检测各组大鼠神经功能缺损评分(mNSS)、脑含水量、缺血半暗带区脑皮质神经元数目及损伤凋亡、脑组织与血清肿瘤坏死因子α(TNF-α)、单核细胞趋化蛋白-1(MCP-1)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平和Bax、PARP、AQP4、AQP9、AKT-FOXO1/3信号通路相关蛋白表达水平。结果与模型组比较,AST-L组、AST-H组缺血半暗带区脑皮质神经元病理损伤减轻,mNSS评分、脑含水量、血清TNF-α、MCP-1及MDA水平、神经元凋亡率、Bax、cleaved PARP、AQP4及AQP9蛋白表达均降低,神经元数目、血清SOD水平、p-AKT/AKT、p-FOXO1/FOXO1及p-FOXO3/FOXO3比值均升高(均P<0.05);与AST-H组比较,AST-H+MK-2206组上述指标水平均呈相反趋势(均P<0.05)。结论AST可通过激活AKT-FOXO1/3信号通路从而抑制MCAO模型大鼠炎性反应及氧化应激,进而减轻其脑水肿及神经元凋亡损伤,并改善神经功能。Aim To investigate the therapeutic effect of total astragalus saponins(AST)on cerebral edema in ischemic model rats by regulating the protein kinase B(AKT)-forkhead box protein O(FOXO)1/3 pathway.Methods SD rats were used to create a middle cerebral artery occlusion(MCAO)model using the thread embolization method and randomly separated into a model group,a AST low-dose group(AST-L,56 mg·kg^(-1)),a AST high-dose group(AST-H,112 mg·kg^(-1))group,a AST-H+MK-2206 group and a sham operation group(all n=10).Neurological severity score(mNSS),brain water content,numbers and apoptosis pathological damage of cortical neurons of ischemia penumbra area,the level of TNF-α,MCP-1,MDA,and SOD in the ischemic penumbra area brain tissue and serum,the expression of Bax,PARP,AQP4,AQP9,and AKT-FOXO 1/3 pathway related proteins in the ischemic penumbra area brain tissue were detected.Results Compared with the model group,the pathological damage of cerebral cortical neurons in ischemic penumbra of rats in the AST-L and AST-H groups was reduced,mNSS score,brain water content,serum TNF-α,MCP-1 and MDA levels,apoptosis rate of neurons,Bax,cleaved PARP,AQP4 and AQP9 protein expression were all decreased(all P<0.05),the number of neurons,serum SOD level,p-AKT/AKT,p-FOXO1/FOXO1 and p-FOXO3/FOXO3 were all increased(all P<0.05).Compared with the AST-H group,the above indexes in the AST-H+MK-2206 group showed an opposite trend(P<0.05).Conclusion AST can inhibit inflammation and oxidative stress in MCAO model rats by activating AKT-FOXO1/3 signal pathway,thereby reducing brain edema and neuronal apoptosis damage,and improving neural function.

关 键 词：黄芪总苷 AKT-FOXO1/3信号通路 缺血性脑卒中 脑水肿 治疗 

分 类 号：R74[医药卫生—神经病学与精神病学] R651.15[医药卫生—临床医学]