Study On The Effects Of Different Exercise Combined With Metformin On AMPK/SIRT1/NF-κB Inflammatory Signaling Pathway In Skeletal Muscle Of Db/db Mice

Objective : This study aims to investigate the effects of different exercise modes combined with metformin on AMPK/SIRT1 / NF-κB inflammatory signaling pathway in skeletal muscle of diabetic mice.The curative effect of different treatment methods was compared to provide theoretical basis for reasonable comprehensive treatment of diabetes in the later stage.Methods : 40 db/db male mice aged 6–8 weeks were randomly divided into metformin control group(C,n = 10),metformin combined with aerobic exercise group(O,n = 10),metformin combined with resistance exercise group(P,n = 10)and metformin combined with aerobic and resistance exercise group(OP,n = 10).Group C was given metformin for 8 weeks;Group O received metformin combined with moderate intensity(60 %maximum speed)aerobic treadmill training for 8 weeks;P group was given metformin combined with moderate intensity(40 % maximum load)tail load ladder training for 8 weeks;OP group received metformin combined with aerobic treadmill and ladder training for 8 weeks.The body weight and fasting blood glucose of mice were detected weekly and recorded.The contents of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)in serum of mice were detected by ELISA.The protein expressions of AMPK / SIRT1 / NF-κB signaling pathway AMPK,SIRT1,NF-κB BP65 and inflammatory cytokines TNF-αand IL-6 in skeletal muscle were detected by Western Blot.Results:1)During the 8-week training,the weight of mice in each group showed a trend of first increase and then decrease.The blood glucose value in group C increased first and then decreased and then tended to be flat.The decline rate in group P was gradually slow from the fifth week,and the decline trend in group O was wavy.The OP group continued to decline steadily every week until the end of training.Before and after training,four groups of mice weight were significantly increased(p<0.01);Blood glucose in group P and OP Significantly decreased(p<0.05),O group was significantly decreased(p<0.01).After 8 weeks of training,the body weight of exercise group(P group,O group,OP group)was significantly lower than that of C group(p<0.05),and the blood glucose was significantly lower than that of C group(p<0.01).Compared with group P,the blood glucose in group O decreased significantly(p<0.05),and the decrease in group OP was the most significant(p<0.01).2)Compared with group C,TC content was significantly decreased in group P(p<0.05);TG content was significantly different in group O(p<0.01);HDL-C content was significantly increased in the P group(p<0.05),especially in the O and OP groups(p<0.01).Compared with P group,TG content in O group decreased significantly(p<0.05);HDL-C content was significantly increased in the O group(p<0.05).3)Compared with C group,the expression of AMPK protein in OP group was significantly increased(p<0.05),and the increase in O group was more obvious(p<0.01).SIRT1 protein expression was significantly increased in the OP group(p<0.05);NF-κBP65 protein expression was significantly decreased in OP group(p<0.05).Compared with group P,AMPK protein expression was increased in group O(p<0.05).4)Compared with group C,the expression of IL-6 protein in group P was significantly increased(p<0.05),and the increase in group O and group OP was more significant(p<0.01).TNF-αprotein expression showed no significant difference between groups.Conclusion:1)Aerobic resistance combined exercise inhibits inflammation and improves skeletal muscle morphology by activating AMPK/SIRT1/NF-κB pathway.At the same time,aerobic resistance combined exercise increases the expression of anti-inflammatory IL-6,and works with AMPK/SIRT1/NF-κB pathway to alleviate skeletal muscle inflammation and reduce blood glucose.2)All the three exercises could improve the lipid metabolism of db/db mice intervened by metformin,but the effect was not ideal.In terms of reducing blood sugar and improving anti-inflammatory effect,aerobic resistance combined group and simple aerobic exercise group were better.Based on the diversity of exercise,aerobic resistance mixed exercise combined with metformin drug intervention is recommended as a comprehensive rehabilitation program for diabetic patients.