| Objective: This study aims to establish a classic D-galactoseinduced Sprague Dawley(SD)rat model of brain aging,and investigate whether 8weeks of aerobic interval exercise can produce neuroprotective effects by affecting mi R-204-5p-mediated inflammatory response in the aging brain frontal lobe.The aim is to provide scientific basis and practical reference for the mechanism of exercise against brain aging.Methods: Forty-five 12-week-old male SD rats were randomly divided into three groups of 15 each: control group(C group),aging group(S group),and aging plus exercise group(SE group).The S and SE groups were intraperitoneally injected with D-galactose for 6 weeks,while the C group was injected with saline only.After modeling,a one-week water maze experiment was conducted to compare the cognitive ability of the model group and the C group.Following the water maze experiment,the SE group received aerobic interval exercise intervention(6 days per week for 8 weeks),while the C and S groups did not exercise.After exercise,samples were taken,and part of the frontal lobe was fixed by perfusion and used for Nissl staining and electron microscopy.Elisa was used to detect SOD activity and MDA content in the frontal lobe,Real-time PCR was used to detect the expression of mi R-204-5p in the frontal lobe of rats,and immunoblotting was used to detect the expression of Sirt1,NF-κB,and IL-6.Results: Water Maze experiment: Before exercise: the incubation period of each group showed a downward trend,but the decline trend of group C was the most obvious and reached the lowest level on the sixth day,and group C was significantly lower than group S and group SE(P<0.01,P<0.01),there was no statistical difference between group S and group SE(P>0.05).The number of crossing the platform in group C was significantly higher than that in group S and group SE(P<0.01,P<0.01).There was no significant difference in the number of platform crossing between group S and group SE(P>0.05).After exercise: the incubation period of each group still showed a downward trend.On the 6th day,the incubation period of group C was still lower than that of group S and group SE and had a significant difference(P<0.01,P<0.05);the incubation period of group SE was lower than that of group S,with a significant difference(P<0.01).The number of platform crossing in group C was significantly different from that in group S and SE(P<0.01,P<0.05).There was a significant difference in the number of crossing platforms between group S and group SE(P<0.01).The results of SOD activity and MDA content detection showed that the SOD activity of group S was significantly decreased compared with group C(P<0.01),but there was no significant difference between group S and group SE(P>0.05).Compared with S group,SOD activity in SE group was significantly increased(P<0.01).Compared with group C,MDA content in group S was significantly increased(P<0.01),but there was no significant difference between group SE and group C(P>0.05).The content of MDA in SE group was significantly decreased compared with that in S group(P<0.01).The Nissner staining showed that the neurons in group C were closely arranged with complete morphology and structure,and the content of Nissner bodies in the cytoplasm was abundant.The neurons in group S were sparsely arranged,the boundaries were not obvious,and the number of Nissner bodies was small.The number of neurons in SE group was less and the number of neurons was less.The results of electron microscopy showed that the microstructure of the frontal lobe of the rats after 8 weeks of aerobic intermittent exercise was changed compared with that of the aging group.The structure of neurons was intact,the number of organelles increased,and the phenomenon of mitochondrial swelling and vacuole decreased.Real-time PCR showed that compared with C group,the expression of mi R-204-5p in the frontal lobe of rats in S group and SE group was increased,and there were significant differences(P<0.01,P<0.01).Compared with group S,the level of mi R-204-5p in the frontal lobe of rats in group SE was significantly down-regulated by aerobic intermittent exercise(P<0.01).Western Blotting results showed that Sirt1 levels in groups S and SE were significantly decreased compared with group C(P<0.01,P<0.01).Compared with S group,Sirt1 level in SE group was significantly increased(P<0.05).Compared with group C,the expression levels of NF-κB and IL-6 in groups S and SE were significantly increased(P<0.01,P<0.01,P<0.01,P<0.01).Compared with group S,the expression levels of NF-κB and IL-6 in the frontal lobe of rats in group SE were significantly decreased by aerobic intermittent exercise(P<0.01,P<0.05).Conclusion:(1)The spatial learning and memory abilities of D-gal aging rats are decreased,frontal lobe neurons are damaged,and neuroinflammatory responses are enhanced.(2)Aerobic intermittent exercise can improve spatial learning and spatial memory ability,increase the number of frontal lobe neurons,and improve chronic inflammation of aging rats.(3)Intermittent aerobic exercise can reduce the level of proinflammatory factors in the frontal lobe of aging rats and reduce the inflammatory response in the frontal lobe,which may be related to the effect of the down-regulation of mi R-204-5p on the expression levels of Sirt1,NF-κB and IL-6. |
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