有氧运动对糖尿病大鼠学习记忆功能、海马突触可塑性及脂联素信号通路的影响

Effects of aerobic exercise on learning and memory functions, hippocampal synaptic plasticity and the adiponectin signaling pathway in diabetic rats

目的探讨有氧运动对糖尿病大鼠学习记忆功能、海马突触可塑性及脂联素信号通路的影响。方法6周龄雄性SD大鼠随机分为空白对照组(NC组)和高脂饮食组,以5周的高脂饮食联合腹腔灌注低剂量链脲佐菌素(STZ)喂养高脂饮食组大鼠,诱导糖尿病大鼠模型,造模成功后分为糖尿病组(DC组)和糖尿病有氧运动组(DM组)。并对DM组大鼠实施了8周有氧跑台锻炼。8周后,用Morris水迷宫试验测定各组大鼠的学习记忆功能,血清相关指标,用高尔基染色观察分析海马区突触的变化,用蛋白免疫印迹法(Western blot)检测大鼠海马组织脂联素、腺苷酸激活蛋白激酶(AMPK)、葡萄糖转运蛋白4(GLUT4)及突触可塑性相关蛋白(SYN)、突触后致密物(PSD-95)的蛋白质表达水平。结果糖尿病大鼠血清空腹血糖(FBG)、糖化血红蛋白(HBA1c)在8周有氧运动后降低(F=69.248、7.017,均P<0.01),血清脂联素和胰岛素在8周有氧运动后升高(F=14.315、6.740,均P<0.05)。海马高尔基染色海马CA3区树突棘数量(F=9.307,P=0.001)、树突棘密度(F=6.734,P=0.008)增加。糖尿病大鼠逃避潜伏期在8周有氧运动后降低(F=13.934,P<0.01),穿越平台次数增加(F=5.864,P=0.023)。糖尿病大鼠海马PSD-95、SYN、脂联素、p-AMPK、GLUT4蛋白表达水在平8周有氧运动后显著增加(F=5.415、15.137、9.687、9.298、27.761,均P<0.05)。结论8周有氧运动可改善糖尿病大鼠的学习记忆功能,其机制可能与运动诱导大鼠海马脂联素/AMPK/GLUT4信号通路的激活,导致其海马突触可塑性增强有关。

Objective To explore the effects of aerobic exercise on learning and memory functions,hippocampal synaptic plasticity and the ADPN signaling pathway in diabetic rats.Methods 6-week-old male SD rats were randomly divided into a blank control group(NC group)and a high-fat diet group,and a rat model for diabetes was induced by feeding rats in the high-fat diet group with a high-fat diet combined with intraperitoneal instillation of low-dose streptozotocin(STZ)for 5 weeks.Rats in the high-fat diet group were further divided into a diabetic group(DC group)and a diabetic aerobic exercise group(DM group)after successful establishment of the model.Rats in the DM group were subjected to aerobic exercise for eight weeks and then the Morris water maze test was conducted to assess learning and memory functions,relevant serum markers were measured,Golgi staining was used to examine synaptic changes in the hippocampus,and Western blot was carried out to detect hippocampal protein expression levels of adiponectin(ADPN),AMP-activated protein kinase(AMPK),glucose transporter 4(GLUT4),synaptic plasticity-related protein synaptophysin(SYN)and postsynaptic density protein 95(PSD-95)for rats in each group.Results Serum FBG and HBA1c in diabetic rats were markedly significantly decreased after 8 weeks of aerobic exercise(P<0.01),and serum ADPN and insulin were significantly increased after 8 weeks of aerobic exercise(P<0.05).When test results from the three groups of rats compared,the F value was 69.248 for FBG,6.740 for INS,7.017 for HBA1C and 14.315 for serum ADPN.The results of the water maze test and hippocampal Golgi staining showed that the escape latency of diabetic rats was highly significantly decreased after 8 weeks of aerobic exercise(P<0.01).The platform crossing times,the number of dendritic branches and the dendritic spine density in the hippocampal CA3 region of diabetic rats were significantly increased after 8 weeks of aerobic exercise(P<0.05).When results from the three groups of rats were compared,the F value was 13.934 for escape latency,5.864 for platform crossing times,9.307 and 6.734 for the number of dendritic branches and the density of dendritic spine in hippocampal CA3 region.Hippocampal PSD-95,SYN,ADPN,p-AMPK,and GLUT4 protein expression levels of diabetic rats were significantly increased(P<0.05)after 8 weeks of aerobic exercise.When results from the three groups of rats were compared,the F value was 15.137 for SYN,5.415 for PSD-95,9.687 for ADPN,27.761 for GLUT4,and 9.298 for p-AMPK.Conclusions Eight weeks of aerobic exercise can improve the learning and memory functions of diabetic rats,and the mechanisms may be related to exercise-induced hippocampal ADPN/AMPK/GLUT4 signaling activation in rats,leading to enhanced synaptic plasticity in the hippocampus.