Effects Of Aerobic Exercise On Oxidative Stress And Apoptosis Indicators In The Kidneys Of Early-aged Mice

Background: As human life expectancy continues to increase,population aging presents growing challenges to clinical practice.Human aging is associated with changes in the molecular structure and function of various organ systems,including the kidney.During aging,the kidneys undergo progressive functional decline and macroscopic and microscopic histological changes that are exacerbated by underlying renal disease or other comorbidities.Physiological changes during normal aging may reduce the ability of the kidneys to repair,thereby predisposing older adults to acute kidney disease,chronic kidney disease,and other types of kidney disease.At present,the treatment of advanced senile renal disease is very difficult.Therefore,it is of great practical significance to seek suitable non-drug means to intervene in renal aging in early aging.As we all know,aerobic exercise can fight the aging of the body and delay the decline of the function of various organ systems.A large number of studies have shown that exercise can delay the aging of organs such as liver and heart by regulating the level of free radical metabolism and apoptosis.However,there are few studies on the effect of aerobic exercise on renal aging.The existing research shows that renal aging is closely related to oxidative stress and apoptosis.Based on this,this study intends to explore the possible molecular mechanism of exercise in delaying renal aging from two aspects of oxidative stress and apoptosis.Objective: The 12-month-old natural aging mice were trained with treadmill for 8weeks to observe the effects of aerobic exercise on renal oxidative stress and apoptosis in natural aging mice.To explore its possible mechanism,in order to provide experimental basis for exercise to delay renal aging.Methods: Eighteen C57BL/6 male mice were used in this experiment,including six 3months old mice(youth control group YC group)and twelve 12-month-old mice.In the experiment,the aging model of natural aging was adopted,and 12-month-old mice were randomly divided into two groups,one was the elderly control group(AC group)and the other was the elderly exercise group(AE group).The elderly exercise group underwent 8-week medium-and low-intensity treadmill training intervention,5 days a week,45 minutes a day.After 8 weeks,the mice were sacrificed by de-neck method,and the kidneys were rapidly isolated,the capsules were removed in low temperature saline,the left kidney was placed in formalin solution,and the right kidney was kept in liquid nitrogen.Morphological and structure of kidneys were observed by Hematoxylin-eosin(HE)staining;biochemical methods were used to detect superoxide dismutase(SOD)activity,malondialdehyde(MDA)content,and monoamine oxidase(MAO)content;Detection of relative expression levels of Bcl-2、Bax and Caspase-3 mRNA in kidney by real-time fluorescence quantitative method.Results: 1.Changes in the appearance of mice: the mice in the YC group were in good mental state,with bright fur,agile movements and normal diet;the mice in the AC group were listless,slow to move,normal diet,lethargy,inc reased grooming behavior,sparse hair,and loss of hair The mice in the AE group were in good mental state,acted more agilely,had a normal diet,and were groomed after exercise.2.Weight results: In the first week,the weight of the mice in the AC group and the AE group was significantly higher than that in the YC group(P<0.01);there was no statistical difference in the weight of mice between AC and AE groups(P>0.05).In the fifth week,the weight of the mice in the AC group and the AE group was significantly higher than that in the YC group(P<0.01);there was no statistical difference in the weight of of mice between AC and AE groups(P>0.05).In the ninth week,the weight of the mice in the AE group was higher than that in the YC group(P<0.05),and there was no statistical difference in the weight of mice between AC and YC groups(P>0.05),there was no statistical difference in the weight of mice between AC and AE groups(P>0.05).3.HE staining results: There was no obvious abnormality in the glomer ulus,no obvious atrophy of the renal tubule,and the renal capsule were normal in each group of mice.The renal interstitium of mice in AC group and AE group was scattered with fibrous connective tissue hyperplasia with chronic inflammatory cell infiltrat ion.4.Biochemical assay results: Compared with the YC group,the renal SOD activity in the AC group decreased,the MDA content increased,and the SOD/MDA value was significantly decreased(P<0.05,P<0.01),but there was no statistical difference in the MAO content(P>0.05).Compared with the AC group,the renal SOD activity in the AE group was increased,and the SOD/MDA value was significantly increased(P<0.05,P<0.01),There was no statistical difference in the content of MDA and MAO(P>0.05).).5.RT-qPCR assay results: Compared with the YC group,the renal Bax mRNA expression in the AC group was significantly increased,the Bcl-2 mRNA expression was significantly decreased(P<0.01),and the Caspase-3 mRNA expression was increased(P<0.05).Compared with the AC group,the renal Bax mRNA and Caspase-3 mRN A expression in the AE group decreased(P < 0.05),while the Bcl-2mRNA expression increased(P < 0.05).Conclusion:(1)During the aging process,the activity of SOD in the kidneys of mice decreased,the content of MDA increased,the value of SOD/MDA decreased significantly,and the level of oxidative stress increased.Aerobic exercise intervention in the early stage of aging can increase SOD activity,significantly increase SOD/MDA value,reduce the level of oxidative stress in aging body,and may delay kidney aging.(2)During the aging process,the expression levels of pro-apoptotic genes Bax mRNA and Caspase-3 mRNA in mouse kidneys were up-regulated,and the expression levels of anti-apoptotic gene Bcl-2 mRNA were down-regulated,which promoted cell apoptosis.Aerobic exercise intervention in the early stage of aging can down-regulate the expression of pro-apoptotic genes Bax mRNA and Caspase-3mRNA,up-regulate the expression of anti-apoptotic gene Bcl-2 mRN A,antagonize renal cell apoptosis,and may delay renal aging.