| Objective:(1)To explore the intervention and interaction of aerobic exercise and Ala-Gln on myocardial fibrosis in type 2 diabetes mellitus.(2)To explore the physiological mechanism of exercise training and Ala-Gln intervention on the formation of myocardial fibrosis in T2DM from the changes of oxidative stress/NF-?B pathway in myocardial tissue.Method:Methods:10 rats were randomly selected as normal control group(NC,n=10)from 80 4-week-old male SD rats,which did not exercise training,fed a standard normal diet.The remaining 70 SD rats were fed high-fat and carbohydrate diet.Six weeks later,the streptozotocin was injected with low-dose(40 mg/kg body weight)in the fasting state.The fasting blood glucose was measured after 7 days,the rats which blood glucose reached 11.1mmol/L were slected as modeling success.And then the type 2 diabetes rats were randomly divided into 4 groups:DM control group(DMC,n=10),DM+ aerobic exercise training group(DME,n=10),DM+ Ala-Gln group(DMAG,n=10)and DM+ aerobic exercise training + Ala-Gln group(DMEAG,n=10),and feed standard normal diet.The DM group's rats did not exercise training.Exercise were used 60 minutes' unloaded swimming,6 times per week.Ala-Gin were irrigationed after 30min the end of each training,the supply dose was 1.5 g/Kg bodyweight,6 times per week.8 weeks later,the fasting blood glucose(FBG),insulin(INS),C peptide(C-P)and glucagon like peptide-1(GLP-1),cardiac troponin I(cTnI)contents and nuclear factor kappa B(NF-?B),transforming growth factor beta-1(TGF-?1),tumor necrosis factor alpha(TNF-?)contents in myocardial tissue were examined by Elisa;the mRNA expression of thioredoxin(Trx),thioredoxin reductase(TR)and collagen fiber ?,? in myocardial tissue were measured by RT-PCR;malondialdehyde(MDA)in myocardial tissue were examined by thiobarbituric acid method;glutathione(GSH),oxidized glutathione(GSSG),contents in myocardial tissue were examined by spectrophotometer;and the morphology and ultrastructure of myocardium tissue were observed.Results:(1)Compared with NC group,in DMC group,the FBG(P<0.05)increased significantly,the serum GLP-1(P<0.01),C-P(P<0.05)contents decreased significantly,INS content increased,but there was no significant(P>0.05).Through the double factor variance analysis,aerobic exercise could decrease the FBG significantly(P<0.01),increase the serum C-P content significantly(P<0.01),the serum INS,GLP-1 contents had some increase,but there were no significant(P<0.05).The supply with Ala-Gln could decrease FBG significantly(P<0.05),increase the serum INS(P<0.05),GLP-1(P<0.05)and C-P(P<0.01)contents significantly.Aerobic exercise combined with Ala-Gln supplement had significantly obvious interaction on increasing the serum INS,C-P and GLP-1 contents(P<0.01),but had no significantly obvious interaction on decreasing FBG content(P>0.05).(2)Compared with NC group,in DMC group,the mRNA expression of type ? collagen fiber(P<0.05)and type ? collagen fiber(P<0.05)increased significantly.Through the double factor variance analysis,aerobic exercise could decrease the expression of type ?,? collagen fiber mRNA in myocardium tissue significantly(P<0.05).The supply with Ala-Gln could decrease the expression of type ? ? collagen fiber mRNA in myocardium tissue significantly(P<0.05).Aerobic exercise combined with Ala-Gln supplement had no significantly obvious interaction on decreasing the expression of type ?,? collagen fiber mRNA(P>0.05).Compared with NC group,in DMC group the myocardial cells myofibril disordered,and appear dissolution phenomenon,Z line distortion;the mitochondria in myocardial cells size ranged,ridge blur,the quantity decreased.In DME and DMAG groups,the myofibrils in myocardial cells and Z line arranged clear,the quantity of mitochondria increased and the shape approximate.DMEAG groups myocardial cells myofibril arranged neatly,muscle filament structure was clear,Z line was clearly and arranged regular,the quantity of mitochondria increased and the ridge was clear.Compared with NC group,in DMC group,the cTnI(P<0.01)contents increased significantly.Through the double factor variance analysis,aerobic exercise could decrease the serum cTnl contents significantly(P<0.01).The supply with Ala-Gln could decrease the serum cTnl(P<0.01)contents significantly.Aerobic exercise combined with Ala-Gln supplement had no significantly obvious interaction on decreasing the serum cTnl contents(P>0.05).(3)Compared with NC group,in DMC group,MDA(P<0.05),GSSG(P<0.01)contents in the myocardium tissue increased significantly(P<0.05),GSH content decreased,but there were no significant(P>0.05),GSH/GSSG ratio decreased significantly(P<0.01),the mRNA expression of TR and Trx in myocardium tissue decreased significantly(P<0.01).Through the double factor variance analysis,aerobic exercise could decrease MDA and GSSG contents in the myocardium tissue significantly(P<0.05),and increase the expression of TR mRNA significantly(P<0.05).GSH content,GSH/GSSG ratio and the expression of Trx mRNA in the myocardium tissue had some increase,but there were no significant(P>0.05).The supply with Ala-Gln could decrease MDA and GSSG(P<0.05)contents in the myocardium tissue significantly,increase the GSH content(P<0.05)and GSH/GSSG ratio(P<0.01)significantly,increase the expression of TR and Trx mRNA in myocardium tissue significantly(P<0.05).Aerobic exercise combined with Ala-Gln supplement had no significantly obvious interaction on decreasing MDA and GSSG contents in the myocardium tissue,and increasing GSH content,GSH/GSSG ratio and the expression of TR mRNA(P>0.05),but had significantly obvious interaction on increasing the expression of Trx mRNA(P<0.05).(4)Compared with NC group,in DMC group,NF-?B,TGF-?1 and TNF-a contents in the myocardium tissue increased significantly(P<0.05).Through the double factor variance analysis,aerobic exercise could decrease NF-?B,TGF-?1 and TNF-a contents significantly(P<0.01).The supply with Ala-Gln could decrease NF-?B(P<0.01),TGF-?1(P<0.01)and TNF-?(P<0.05)contents significantly.Aerobic exercise combined with Ala-Gln supplement had significantly obvious interaction on decreasing TGF-?1(P<0.01)and TNF-?(P<0.05),but had no significantly obvious interaction on decreasing NF-?B contents(P>0.05).Conclusion:(1)In this study T2DM model was successful,simple aerobic exercise and Ala-Gln could promote the secretion of INS in T2DM rats and had a significant role on control FBG,aerobic exercise combined with Ala-Gln supplement was more effective on decreasing the FBG levels in T2DM rats.(2)After T2DM model were successfully established for 8 weeks,the fibrillation was happened in myocardial tissue in some degree,and myocardial cells had a modest injury.Aerobic exercise or Ala-Gln supplement had an effective inhibitor for the formation of myocardial fibrosis in T2DM rats,and the aerobic exercise combined with Ala-Gln was more effective.(3)The most important mechanism of the form of myocardial fibrosis in T2DM rats was that the decrease of function of Trx system,lead to oxidative stress,and promote the secretion of inflammatory factors.Aerobic exercise and Ala-Gln could improve the function of thioredoxin system in T2DM myocardial tissue,and reduce the production of MDA,reducing the secretion of inflammatory factor in myocardial tissue,inhibit the occurrence and development of myocardial fibrosis in T2DM rats. |
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