基于胰岛素抵抗探讨有氧运动改善阿尔茨海默病及其作用机制的研究进展

Research Progress on the Improvement of Alzheimer’s Disease and Its Mechanism of Action through Aerobic Exercise Based on Insulin Resistance

通过梳理有氧运动基于改善胰岛素抵抗(insulin resistance, IR)延缓和改善阿尔茨海默病(Alzheimer’s disease, AD)及其机制的研究进展,研究发现,IR可导致脑内胰岛素信号传导障碍、糖代谢紊乱、脂质异位沉积、内质网应激障碍、血管系统损伤,协同促进了AD发生。有氧运动可通过以下机制改善IR,进而延缓AD:有氧运动增强磷酸肌醇3-激酶/蛋白激酶B(phosphatidylinositol 3-kinase/protein kinase B, PI3K/Akt)信号通路,提升沉默信息调节因子(silent information regulator 1,SIRT1)水平,调节mTOR信号通路增强自噬;提高大脑糖代谢水平,改善糖代谢紊乱,增强胰岛素敏感性,改善神经突触损伤;增强机体的脂代谢水平,减少脑内脂质异位沉积;降低IR和AD引起的内质网应激,激活神经元自噬,减少β-淀粉样蛋白(β-amyloid, Aβ)沉积,改善突触可塑性;诱导血管抗氧化路径减少炎症和氧化应激,促进毛细血管的生成,改善大脑血液灌注。

Through the review of research progress of aerobic exercise based on improving insulin resistance(IR)to delay and improve Alzheimer's disease(AD)and its mechanism,this study have found that IR can lead to impaired insulin signaling,glucose metabolism disorders,lipid ectopic deposition,endoplasmic reticulum stress disorders,and vascular system damage in the brain,which synergistically promot the occurrence of AD.Aerobic exercise can improve IR and delay AD through following mechanisms:Aerobic exercise can enhance the phosphoinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway,increase the level of silent information regulator 1(SIRT1),regulate the mTOR signaling pathway,and enhance autophagy;improve brain glucose metabolism levels,alleviate glucose metabolism disorders,enhance insulin sensitivity,and alleviate synaptic damage;enhance the body’s lipid metabolism level and reduce ectopic fat deposition in the brain;reduce endoplasmic reticulum stress caused by IR and AD,activate neuronal autophagy,reduceβ-amyloid peptide(Aβ)deposition,and improve synaptic plasticity;induce vascular antioxidant pathways,reduce inflammation and oxidative stress,promote generation of capillaries,and improves cerebral blood perfusion.