| Objective:To observe the effects of aerobic exercise combined with curcumin intervention on insulin,glucose metabolism and other related indexes in T2 DM rats induced by high-sugar and high-fat diet combined with low-dose STZ,and analyze the prevention and treatment effect of aerobic exercise combined with curcumin intervention on T2 DM based on AMPK/Rab5/GLUT4 signaling pathway.To explore whether the effect of combined intervention is better than that of aerobic exercise and curcumin alone,in order to provide scientific basis and theoretical basis for the treatment of T2 DM.Methods:In this study,40 male SD rats were selected,and 6 of them were randomly divided into normal group(group N)and the remaining 34 were randomly divided into diabetes model group(group DM).In DM group,a T2 DM model was established by one-time intrabitoneal injection of streptozotocin(STZ)on the basis of high-sugar and high-fat diet.Random blood glucose ≥ 16.7 was the standard for modeling.After successful modeling,DM group was randomly divided into model group(M),aerobic exercise group(O),curcumin group(C)and aerobic exercise +curcumin group(O+C),with 6 animals in each group.After one week of adaptive training,the rats in group O and group O+C were given aerobic exercise intervention.The formal exercise program was as follows: slope 0°,warm-up activities 15 m/min,10 min;Formal exercise 20 m/min,45 min;Resume activity 15 m/min,5min,6days/week,a total of 8 weeks.Group C and group O+C were given curcumin intragastric administration at a dose of 200mg/(kg·d)for 6 days/week for 8 weeks.After 8 weeks,body weight,fasting blood glucose(FBG)and fasting serum insulin(FINS)were measured,and oral glucose tolerance test(OGTT)was performed,and the area under the curve of glucose tolerance test(AUCOGTT)was calculated.The histopathological changes of gastrocnemius were observed by HE staining.The glycogen content was observed by PAS glycogen staining.The content of glucose transporter 4 in gastrocnemius of rats was detected by immunohistochemistry.The expression levels of AMPK,Rab5 and GLUT4 in gastrocnemius of rats were determined by Western blot.Results:(1)Before the formal experiment,through the adaptive feeding of the rats for a week,it was known that 40 rats had tight and glossy fur color,sensitive response to external stimuli,good desire to explore and relatively docile.With the progress of the experiment,the overall state of group M was sluggish,the hair color was messy and dark,the response to external stimuli was slow,and the movement was slow.After 8weeks of intervention,the overall mental state,fur color and motor flexibility of rats in groups O,C and O+C were improved compared with those in group M.(2)After intervention,the results of body weight of rats in all groups showed that:compared with group N,group M,group O,group C and group O+C had very significant differences(P < 0.01);Compared with group M,group O and group O+C had a very significant difference(P < 0.01),group C had a significant difference(P <0.05);There was no significant difference in group O+C compared with group O and group C(P > 0.05).(3)After intervention,the fasting blood glucose results of all groups showed that:compared with group N,group M,group O,group C and group O+C had very significant differences(P < 0.01);Compared with group M,group O had a significant difference(P < 0.05),group C and group O+C had a very significant difference(P <0.01);There was no significant difference in group O+C compared with group O and group C(P > 0.05).(4)AUCOGTT experimental results showed that: compared with group N,groups M,O,C and O+C had very significant differences(P < 0.01);Compared with group M,group O and group C had significant difference(P < 0.05),group O+C had very significant difference(P < 0.01);Compared with group O and group C,group O+C had significant difference(P < 0.05).(5)The results showed that FINS levels in M,O,C and O+C groups were significantly higher than those in N group(P < 0.01);Compared with M group,FINS levels in groups O,C and O+C were significantly decreased(P < 0.01).Compared with group O,group O+C was significantly lower,with a significant difference(P <0.01),and group O+C was significantly lower than group C,with a significant difference(P < 0.05).(6)The results of HE staining showed that the muscle fibers of gastrocnemius muscle in group N were arranged regularly,with uniform size and shape of muscle cells and clear boundaries;Compared with group N,the myocytes in group M were arranged loosely,some cells showed swelling,fibrodegeneration or inflammatory cell infiltration,and showed pathological injury.Compared with the M group,the myocytes in groups O,C and O+C were arranged neatly,the number of inflammatory cells decreased,and the tissue morphology of gastrocnemius was significantly improved.Among them,group O+C is more significant.(7)PAS glycogen staining showed that a large purplish red staining area was visible in the gastrocnemius of group N,indicating that the gastrocnemius contained a large amount of glycogen;There were few purplish red glycogen staining areas in group M,suggesting that the glycogen content in gastrocnemius of rats was reduced.After intervention,a small number of purplish red staining areas were observed in group C,Group O and group O+C,suggesting an increase in glycogen content in the gastrocnemius of rats.Among them,group O+C is more significant.(8)Immunohistochemical results showed that GLUT4 expression of the target protein in gastrocnemius of all groups was in the cell membrane,and the color was brown-yellow particles,which had a very significant difference compared with group N,group M,group O and group C(P < 0.01),and group O+C had a significant difference(P < 0.05).Compared with group M,group O,group C and group O+C were significantly different(P < 0.01).There was no significant difference between group C and group O+C compared with group O(P > 0.05).Compared with group C,group O+C had significant difference(P < 0.05),but group O had no significant difference(P > 0.05).These results suggest that aerobic exercise and curcumin can significantly increase GLUT4 expression in T2 DM rats,and the combined effect of both is better.(9)Western Blot test results: Compared with group N,the expression of histone in group M,group O and group C was significantly decreased(P < 0.01),and that in group O+C was decreased(P < 0.05).Compared with group M,histone expression in group O and C was increased(P < 0.05),and histone expression in group O+C was significantly increased(P < 0.01).Compared with groups O and C,the histone content of O+C was increased(P < 0.05).The comparison of Rab5 protein expression among groups showed that compared with group N,histone expression in groups M,O and C was significantly decreased(P < 0.01),and decreased in group O+C(P < 0.05);compared with group M,histone expression in groups O and C was increased(P <0.05),and histone expression in O+C was significantly increased(P < 0.01);Compared with groups O and C,the content of Rab5 protein in gastrocnemius of rats in O+C group was increased(P < 0.05).Compared with group N,the GLUT4 protein content of gastrocnemius in groups M,O,C and O+C was significantly decreased(P< 0.01).Compared with group M,GLUT4 protein content of gastrocnemius in groups O and C was increased(P < 0.05),and significantly increased in group O+C(P <0.01);Compared with groups O and C,GLUT4 protein content in gastrocnemius of rats in group O+C was increased(P < 0.05).Conclusions:(1)Both aerobic exercise and curcumin intervention can improve the weight,FBG,OGTT and ITT of T2 DM rats,increase the tolerance to glucose load of rats,and regulate the disorder of skeletal muscle glucose metabolism,and the combined effect of both is better.(2)Both aerobic exercise and curcumin intervention can improve the skeletal muscle morphological structure and increase the skeletal muscle glycogen content in T2 DM rats,and the combined effect is better.(3)Aerobic exercise and curcumin can improve T2 DM through AMPK/Rab5/GLUT4 signaling axis,and the combined effect of the two is better,which may be related to the improvement of skeletal muscle glucose metabolism. |
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