Effect Of Aerobic Exercise On Learning And Memory Function Of Diabetic Rats And Its Mechanism

Objective: In this study,a rat model of type 2 diabetes(T2DM)was induced on the basis of a 5-week high-fat diet combined with intraperitoneal injection of 1% streptozotocin(STZ).After the model was successfully established,some rats were selected for a period of 8 weeks.Aerobic exercise intervention.On the one hand,the Morris water maze experiment was used to detect the learning and memory function of T2 DM rats and the intervention effect of aerobic exercise.On the other hand,Golgi staining was used to observe the structural changes of hippocampal synapses in T2 DM rats,and to detect synaptic plasticity-related proteins(synapsin(SYN),postsynaptic compact(PSD-95))and serum,Changes in hippocampal adiponectin(ADPN)and its downstream AMP-dependent protein kinase(AMPK)/glucose transporter 4(GLUT4)signaling pathways,and explore its possible mechanisms for improving cognitive dysfunction in T2 DM.It is expected to provide a new target for the prevention and treatment of cognitive dysfunction in diabetic patients.Methods: Six-week-old male SD rats were selected and randomly divided into a blank control group(NC group and high-fat diet group.Rats in the high-fat diet group received 5-week high-fat diet combined with intraperitoneal injection of low-dose streptozotocin T2 DM rat model induced by STZ,and successfully modeled T2 DM rats were randomly divided into diabetes model group(Diabetes control group;DC group)and diabetic aerobic exercise group(Diabetes moderate intensity exercise group;DM group).The DM group received aerobic treadmill training for8 weeks,6 days a week,60 minutes each time,a total of 8 weeks of training.The rats were subjected to a 7-d Morris water maze experiment on the day after the last training.After the exercise intervention,the Morris water maze experiment was used to test the learning and memory function of each group of rats;After fasting for 12 hours,intraperitoneal injection of 10% chloral hydrate to anesthetize the thoracic aorta with a dose of 2.5ml/kg.After the blood is taken,the head is quickly decapitated,and the left and right hippocampus are separated;the serum fasting blood glucose(FBG)is detected by the glucose oxidase method,Enzyme-linked immunosorbent assay(Elisa)method to detect serum insulin(INS)and adiponectin(ADPN),colorimetric method to detect serum glycosylated hemoglobin(GHb);Golgi staining was used to observe and analyze the pathological changes of synapses in the hippocampus.Western blot was used to detect the protein expression levels of ADPN,AMPK,and GLUT4 in the hippocampus and the protein expression levels of synaptic plasticity-related proteins(PSD-95,SYN).The experimental data obtained between the two groups used independent sample t test.P<0.05 indicates that the difference is significant,and P<0.01 indicates that the difference is extremely significant.Results: 1)Compared with the NC group,the FBG,HBA1 c,and HOMA-IR of the DC group increased significantly(P<0.01),and the serum adiponectin and INS decreased significantly(P<0.01);Compared with the DC group,FBG,HBA1 c,and HOMA-IR in the DM group were significantly reduced(P<0.01),and the serum INS and adiponectin were significantly increased(P<0.05,P<0.01);2)and NC Compared with the DC group,the escape latency of rats in the DC group was significantly increased(P<0.01,P<0.05);compared with the DC group,the escape latency of the DM group was significant from day 1 to day 3 and day 5.Decrease(P<0.01,P<0.05);Compared with the NC group,the number of crossings in the DC group was significantly reduced(P<0.05),and compared with the DC group,the number of crossing platforms in the DM group was significantly increased(P<0.05);3)Compared with the NC group,the number of neuron dendritic branches and dendritic spine density in the hippocampal CA3 area of the DM group were significantly reduced(P<0.01);compared with the DC group,the hippocampal CA3 area of the DM group The number of neuron dendritic branches and dendritic spine density increased significantly(P < 0.01,P < 0.05);4)Compared with the NC group,the expression of SYN and PSD-95 protein in the hippocampus of the DC group was extremely significant Decrease(P < 0.01);Compared with DC group,SYN and PSD-95 protein expression in hippocampus of DM group increased significantly(P<0.01,P < 0.05);5)Compared with NC group,DC ADPN,GLUT4,and p-AMPK protein expressions in the hippocampus of the DM group were significantly reduced(P<0.01);compared with the DC group,the ADPN,GLUT4,and p-AMPK protein expressions in the hippocampus of the DM group increased significantly(P<0.01,P<0.05).Conclusion:(1)The hippocampal learning and memory function of T2 DM rats was significantly decreased.Aerobic exercise for 8 weeks can improve the hippocampal learning and memory function of T2 DM rats.(2)8-week aerobic exercise can improve hippocampal synaptic plasticity by enhancing the ADPN/AMPK/GLUT4 pathway in the hippocampus of T2 DM rats,thereby enhancing the learning and memory function of the hippocampus of T2 DM rats.