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.
Abstract
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.
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