有氧运动调节糖尿病小鼠海马组织miR-126表达改善认知障碍的机制  

Mechanism of aerobic exercise regulated miR-126 expression in the hippocampus of diabetic mice to improve cognitive impairment

作　　者：马亦潇 宣俊杰 杨翼[2] 柳华[2] MA Yixiao;XUAN Junjie;YANG Yi;LIU Hua(Physical Monitoring and Chronic Disease Intervention Research Center,Wuhan Sports University,Wuhan 430079,Hubei,China;College of Sports Medicine,Wuhan Sports University,Wuhan 430079,Hubei,China)

机构地区：[1]武汉体育学院体质监测与慢病干预研究中心,湖北武汉430079 [2]武汉体育学院运动医学院,湖北武汉430079

出　　处：《陕西师范大学学报（自然科学版）》2023年第5期112-122,共11页Journal of Shaanxi Normal University：Natural Science Edition

基　　金：国家自然科学基金(81700280,81970261)。

摘　　要：为明确有氧运动改善糖尿病小鼠认知功能的作用机制,研究了有氧运动对糖尿病小鼠学习记忆能力,海马组织的形态学、炎症反应、细胞凋亡及miR-126相关通路的影响。将12只15周龄糖尿病雄性小鼠随机分为空白对照组(DC组,6只)、有氧运动组(DE组,6只),同周龄正常小鼠为正常对照组(MC组,6只)。DE组进行8周跑台运动干预,DC组和MC组不做干预。8周运动后,进行水迷宫定向导航和空间探索实验评估其学习记忆能力。结果表明:与DC组相比,有氧运动8周后DE组血糖、血清胰岛素水平显著降低(P<0.05);水迷宫定向导航结果显示DE组逃避潜伏期显著降低(P<0.05),游泳速度、目标象限时间百分比均显著增高(P<0.01)。较之DC组,HE染色后可见DE组锥体细胞排列整齐、紧密,细胞层数较多,细胞核大小匀称;免疫荧光染色显示DE组海马DG区、CA1区、CA3区神经元数量显著增加(P<0.05)且胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)中胶质细胞活化面积显著下降(P<0.01)。进一步分析发现小鼠第4天逃避潜伏期、目标象限时间百分比、游泳速度和miR-126表达具有显著性相关(P<0.01)。与DC组比较,DE组海马组织的磷酸化Tau蛋白(phosphory protein tau,p-tau)、β-淀粉样蛋白(amyloidβ-protein,Aβ)、Bax和Caspase-3表达显著降低(P<0.05),Bcl-2显著升高(P<0.05),miR-126下游的HMGB1蛋白以及炎症相关蛋白:细胞外调节蛋白激酶1/2(extracellular regulated protein kinases1/2,ERK1/2)、糖基化终产物受体(receptor for advanced glycation end products,RAGE)、基因高迁移率族蛋白B1(high mobility group protein,HMGB1)、核因子-κB(nuclear factor-κB,NF-κB)显著降低(P<0.05)。研究结果说明8周有氧运动改善糖尿病小鼠认知功能,降低海马组织的细胞凋亡和炎症反应,其机制可能与增加海马组织miR-126含量、抑制HMGB1和NF-κB蛋白表达有关。The learning and memory abilities,hippocampal morphology,inflammatory response,apoptosis,and miR-126/HMGB1/NF-κB pathway in hippocampus of db/db mice were evaluated to explore the mechanism of aerobic exercise improving cognitive function in diabetic mice.A total of 15 week old diabetic male mice were randomly divided into a blank control group(DC group,n=6),an aerobic exercise group(DE group,n=6),and a normal control group(MC group,n=6)for the same age m/m mice.The DE group underwent an 8 week treadmill exercise intervention,no interventions were done in the DC group and MC group.After 8 weeks of exercise,spatial exploration experiments were performed to evaluate learning and memory ability in morris water maze.The results showed that compared to the DC group,blood glucose and serum insulin levels were significantly decreased in the DE group after 8 weeks of aerobic exercise(P<0.05).The directed navigation test showed that the escape latency in the DE group was significantly decreased in morris water maze(P<0.05),and both the swimming speed and the percentage of target quadrant time were significantly increased(P<0.01).Compared with the DC group,HE staining showed that pyramidal cells in the DE group were arranged neatly and tightly,the number of cell layers was higher,and the size of the nucleus was homogeneous.Immunofluorescence staining showed a significant increase in the number of neurons(P<0.05)and a significant decrease in the area of glial fibrillary acidic protein(GFAP,glial fibrillary acidic protein)glial activation(P<0.01)in the DG,CA1 and CA3 regions of the hippocampus in the DE group.The correlations between the cognitive function and the escape latency,percentage of time in the target quadrant,swimming speed and miR-126 expression on day 4 in mice were confirmed(P<0.01).The hippocampal tissue of the DE group contained p-tau,Aβ,Bax and caspase-3 were significantly decreased(P<0.05),Bcl-2 was significantly increased(P<0.05),and miR-126 down stream protein HMGB1 as well as inflammation related prote

关 键 词：有氧运动 糖尿病认知障碍 MIR-126 炎症 

分 类 号：G804.2[文化科学—运动人体科学]