目的:探讨有氧运动对肥胖大鼠海马组织tau蛋白磷酸化水平及其调控通路PI3K/Akt的影响,为揭示运动改善肥胖导致的神经系统功能紊乱提供一定的理论依据.方法:3周龄雄性SD大鼠随机分为高脂饮食组和正常饮食组,分别以高脂饲料和普通饲料饲养12周.随后高脂饮食组大鼠随机分为高脂安静组(HF-Sed组)和高脂运动组(HF-Ex组).正常饮食组大鼠随机分为正常安静组(ND-Sed组)和正常运动组(ND-Ex组).HF-Ex组和ND-Ex组大鼠进行为期8周的跑台训练.训练结束后48小时,分离两侧海马组织.通过Western blot检测各组大鼠海马组织中tau、GSK3β、PI3K和Akt蛋白含量及其磷酸化水平.结果:经过12周的饲养后,高脂饮食组大鼠中有55％符合肥胖大鼠建模成功条件.经过8周跑台训练后,HF-Sed组tau蛋白的磷酸化水平显著高于ND-Sed组;而HF-Ex组tau蛋白的磷酸化水平却显著低于HF-Sed组.另外,HF-Sed组GSK3β Ser9位点的磷酸化水平显著低于ND-Sed组,Tyr216位点的磷酸化水平显著高于ND-Sed组,说明HF-Sed组GSK3β激酶活性高于ND-Sed组;而经过8周跑台训练,HF-Ex组GSK3β Ser9位点的磷酸化水平显著高于HF-Sed组,Tyr216位点的磷酸化水平显著低于HF-Sed组,说明HF-Ex组GSK3β激酶活性受到抑制.此外HF-Sed组PI3K p110、p85亚基蛋白含量和AktThr308、Ser473位点的磷酸化水平显著低于ND-Sed组,说明HF-Sed组PI3K/Akt通路活性受到抑制;而HF-Ex组PI3K p110、p85亚基蛋白含量和Akt Thr308、Ser473位点的磷酸化水平显著高于HF-Sed组,说明HF-Ex组该通路活性增强.结论:肥胖能够诱导大鼠海马组织tau蛋白磷酸化水平上升,而有氧运动通过提高肥胖大鼠海马组织PI3K/Akt信号通路活性,抑制GSK3β的激酶活性,从而降低了tau蛋白的磷酸化水平,对于延缓脑内神经纤维缠结的形成,防治肥胖导致的神经系统退行性疾病有积极作用.“,”Objective To investigate the effects of aerobic exercise on tau phosphorylation and PI3K/ Akt pathway in the hippocampus of obese rats,and provide some theoretical basis for physical activity improving obesity-related neurological disorders.Methods Male Sprague-Dawley rats aged 3 weeks were randomly assigned to either a high-fat or a normal diet protocol for 12 weeks.Animals submitted to the high-fat diet were further divided into two groups:a sedentary group (HF-Sed) and an exercise group (HF-Ex).The rats fed the normal diet were also divided into a sedentary group (ND-Sed)and an exercise group (ND-Ex).The rats in the HF-Ex and ND-Ex groups underwent a treadmill training for 8 weeks.Then the hippocampus was isolated at 48h after the last exercise.The protein and phosphorylation levels of tau,glycogen synthase kinase 3β (GSK3β),phosphoinositide 3-kinase (PI3K) and Akt were assayed using Western blotting.Results After 12 weeks of feeding,55％ of rats in the high-fat diet group reached the conditions for the obesity model.After 8 weeks of treadmill exercises,in the HF-Sed group the phosphorylation level of tau was significanlty higher than that in the ND-Sed group,while in the HF-Ex group that was significantly lower than the HF-Sed group.Moreover,in the HF-Sed group the phosphorylation level of GSK3β Ser9 was significantly lower,and the phosphorylation level of GSK3β Tyr216 was significantly higher than the ND-Sed group,indicating the activity of GSK3β was significantly higher than the ND-Sed group.However,after 8 weeks of treadmill exercise,in the HF-Ex group the phosphorylation level of GSK3β Ser9 was signfiicantly higher,and the phosphorylation level of GSK3β Tyr216 was signficanlty lower than the HF-Sed group,indicating significantly lower activity of GSK3β than the HF-Sed group.Then,in the HF-Sed group the protein levels of PI3K p110 and p85 subunits,and the phosphorylation levels of Akt Thr308 and Ser473 were significantly lower than those in the ND-Sed group,indicating inhibited activity of the PI3K/Akt pathway.However,in the HF-Ex group the protein levels of PI3K p110 and p85 subunits and the phosphorylation levels of Akt Thr308 and Ser473 were significanlty higher than those in the HF-Sed group,showing the activity of PI3K/Akt pathway was enhanced.Conclusion Obesity induces tau hyperphosphorylation in the rats hippocampus and long-term aerobic exercises can reduce tau hyperphosphorylation by increasing PI3K/Akt pathway activity and inhibiting GSK3β activity.It has a positive effect on delaying the formation of neurofibrillary tangles and improving obesity-related neurological disorders.