| Background and research purposes:Type 2 diabetes is an endocrine and metabolic disease.The prevalence of type 2 diabetes is increasing year by year in the global context and it is one of the major chronic diseases that endanger human health.The liver is the main metabolic organ of the body,and its lipotoxicity under the action of diabetes can worsen the condition of diabetes,and improving hepatic lipotoxicity plays an important role in the treatment of diabetes.In recent years,the integration of physical medicine is a research hotspot and development trend in the treatment of diabetes,therefore,In this study,aerobic interval training combined with liraglutide was used to intervene in diabetic rats,observed changes in symptoms of liver toxicity grease,and explore the possible mechanism of intervention,in order to broaden the clinical treatment of diabetes,provide a theoretical basis and practical guidance.Research Materials and Methods:60 eight-week-old Wistar male rats,weighing 200 ± 20 g were selected.They were randomly divided into normal control group(C group)and diabetic model group.The latter is a diabetic rat model that is replicated by a high-sugar-high-fat diet and intraperitoneal injection of low doses of streptozotocin(STZ,30 mg/kg).The criteria for successful replication in a diabetic rat model are: two consecutive fasting blood glucose >11.1 mmol/L after STZ injection.Two weeks after the model was stabilized,exercise and drug intervention was performed.The diabetic rats were randomly divided into diabetic group(D group),aerobic interval training intervention group(DE group),liraglutide-treated group(DL group),aerobic interval training combined with liraglutide group(LE group),8 rats in each group.The aerobic interval training program of DE group and LE group was 10 min warm-up exercise,7min?4 intensity was 85%-90% VO2 max exercise and 3min?4 intensity was 50%-60% VO2 max exercise,10 min finishing exercise.Aerobic interval training was 5 days a week for a total of 8 weeks.DL group and LE group dosing regimen was 0.2mg / kg / d,D group was injected with the same volume of saline for a total of 8 weeks.During the experiment,the fasting blood glucose and body weight of rats were recorded every two weeks.After 8 weeks' intervention,the levels of fasting blood glucose(FBG),total cholesterol(TC),triglyceride(TG),alanine transaminase(ALT)and aspartate transaminase aminotransferase(AST)levels were detected by Enzymatic method.Serum fasting serum GLP-1,serum fasting insulin(FINS),free fatty acid(FFA)and diacylglycerol(DAG)content in Liver tissuewere detected by ELISA;Calculate insulin resistance index(HOMA-IR)and islet beta cell function index(HOMA-?).After the experiment,some liver tissues were fixed with paraformaldehyde for HE staining and oil red O staining to observe histomorphological changes.Western blotting was used to detect the levels of FAT/CD36,CPT-1A,PPARa and GLP-1R protein expression.Research result:(1)Aerobic interval training combined with liraglutide alone and combination of the two can reduce blood glucose and lipids level in diabetic rats,mainly as fasting blood glucose,total cholesterol,and triglyceride decrease(P<0.05),and the effect of exercise and drug combination was numerically better than that of intervention alone,but it was not statistically significant;at the same time,Aerobic interval training and liraglutide increased serum fasting insulin levels(P<0.01),insulin resistance index(P<0.05),and ?-cell function index of diabetic rats(P<0.05),and the effect of combined the two is better(P<0.01).(2)Aerobic interval training,liraglutide and the combination of the two can improve the liver function damage in diabetic rats,showing that the levels of ALT and AST in serum decreased significantly(P<0.01),and exercise combined drugs were more effective;At the same time,morphological observations show that the combination of the two can significantly reduce the changes in the morphology of liver cells.(3)Aerobic interval training,liraglutide,and their combination can reduce hepatic lipid accumulation in diabetic rats,showing a significant decrease in free fatty acid and diacylglycerol content in liver tissue(P<0.01),and exercise combined drugs were more effective,but there was no statistical significance.At the same time,morphological observation showed that the combination of the two could significantly reduce the lipid content in liver cells.(4)Aerobic interval training with liraglutide and their combination both reduced hepatic FAT / CD36 protein expression and increased the expression of CPT-1A protein in liver of diabetic rats(P<0.05 or P<0.01);aerobic interval training,liraglutide and their combination can increase hepatic PPAR? protein expression in diabetic rats(P<0.01);liraglutide and its combination with aerobic interval training can increase expression of GLP-IR protein in liver of diabetic rats(P<0.05 or P<0.01).Research conclusion:(1)In this study,a high-sugar,high-fat diet and low-dose intraperitoneal injection of streptozotocin(30 mg/kg)was successfully used to replicate type 2 diabetes.(2)Aerobic interval training combined with liraglutide can significantly reduce blood glucose and lipid levels in diabetic rats,improve insulin resistance,improve liver function in diabetic rats,reduce liver cell pathological damage,reduce lipid accumulation in the liver,and relieve hepatic lipotoxicity in diabetic rats.(3)The molecular mechanism of aerobic interval training in combination with liraglutide to improve hepatic lipotoxicity in diabetic rats: On the one hand,aerobic interval training combined with liraglutide activated liver PPAR?,increased PPAR? expression,and then decreased the expression of CD36,increased The expression of CPT1A;on the other hand,liraglutide up-regulated liver GLP-1R protein expression,both of which are jointly regulated and realized. |
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