Effect Of Aerobic Exercise Combined With Curcumin On Liver ERS In Rats With T₂DM Combined With NAFLD

1.ObjectiveType 2 diabetes mellitus and nonalcoholic fatty liver disease often co-occur and interact with each other.The endogenous reticulum stress and its induced apoptosis play an important role in the generation and development of these two cells.However,as there is no uniform treatment plan for the combination of the two in clinical practice,this study combined exercise with drugs to observe the effects of aerobic exercise combined with curcumin intervention on the expression levels of GRP78,CHOP and Caspase-12 in the liver of rats with type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease,combined with the observation of liver pathological morphological changes.To understand the mechanism of aerobic exercise combined with curcumin in the treatment of type 2 diabetes mellitus with non-alcoholic fatty liver disease,and to provide a theoretical basis for the establishment of a sound treatment plan.2.MethodsAfter one week of adaptive feeding,40 SD rats were divided into blank group and model group,which were fed ordinary diet and high-sugar and high-fat diet respectively.After 8 weeks,STZ was injected into the model group to induce type 2diabetes model.Then,3 successful diabetic rats were randomly selected to observe the pathological morphology of the liver,and it was determined that the diabetic rats had a non-alcoholic fatty liver disease model.After the successful establishment of the model,they were randomly divided into model group,aerobic exercise group,curcumin group and aerobic exercise combined curcumin group,with 6 animals each.Aerobic exercise group and aerobic exercise combined with curcumin group were given aerobic exercise intervention.Specific program: The rats underwent adaptive training for a week.The training intensity was 15m/min and the training time was10 min on the first day,and the training intensity was gradually increased by 1-2m/min and the training time was increased by 5-10 min /d until the maximum speed was20m/min and the maximum duration was 45 min.The formal training speed is10m/min,the time is 10 min,and the activity is ready.20m/min,time 45 min,official activities;10m/min,time 5min,sorting activity,6 days/week,intervention for 8 weeks;Curcumin group and aerobic exercise combined with curcumin group were given curcumin intragastric administration at a dose of 200mg/(kg·d)for 6 days/week for 8weeks.48 hours after the training,fasting blood glucose(FBG)was measured by weight.Blood was collected from the apex of the heart and blood biochemical indexes were detected.Liver slices were collected,and the pathological morphology of liver was detected by HE staining and oil red O staining.The expression levels of GRP78,CHOP and Caspase-12 in liver of rats were detected by Western Blot.3.Results3.1 Weight changes of rats in each groupCompared with the blank group,the body weight of model group,aerobic group,curcumin group and aerobic ginger group decreased significantly(P < 0.01).Compared with model group,body weight of aerobic group,curcumin group and aerobic plus ginger group increased significantly(P < 0.05).Compared with aerobic group and curcumin group,the body weight of aerobic plus ginger group increased,but there was no significant difference(P > 0.05).3.2 Changes of liver index in each groupCompared with the blank group,the liver index of the other groups increased,with a very significant difference(P < 0.01),the liver index of the aerobic ginger group increased,but there was no significant difference(P > 0.05);Compared with model group,the liver index of aerobic group,curcumin group and aerobic plus ginger group decreased significantly(P < 0.01).Compared with aerobic group and curcumin group,the liver index of aerobic plus ginger group decreased significantly(P < 0.05).3.3 Pathological changes of liver tissue in each group(1)HE staining: After establishing the model,three rat hepatocytes showed different degrees of steatosis.After treatment,there was no significant liver steatosis in the blank group.The liver tissue of the model group showed diffuse steatosis.Liver steatosis was alleviated in aerobic group,curcumin group and aerobic plus ginger group.(2)The results of oil red O staining showed that there were only a few fat droplets in the blank group;A large number of lipid droplets were observed in hepatocytes of model group.The red lipid drops in liver cells of rats in aerobic group,curcumin group and aerobic plus ginger group were significantly reduced.(3)Fat drop positive area ratio: the value of the model group was significantly increased,and the value of the aerobic group,curcumin group and aerobic plus ginger group were decreased to varying degrees,and the decrease of the aerobic plus ginger group was the most significant.3.4 Changes of blood biochemical indexes of rats in each groupCompared with blank group,TC,TG,AST,ALT,LDL,FBG and FINS were increased in model group,aerobic group,curcumin group and aerobic plus ginger group,while HDL was decreased.Compared with model group,TC,TG,AST,ALT,LDL,FBG and FINS were decreased in aerobic group,curcumin group and aerobic plus ginger group,while HDL was increased.Compared with aerobic group and curcumin group,TC,TG,AST,ALT,LDL,FBG and FINS in aerobic ginger group were decreased,while HDL was increased.3.5 Western Blot results(1)GRP78: Compared with blank group,the expression level of histone in model group and aerobic group increased,with a very significant difference(P < 0.01);the expression level of curcumin histone increased,with a significant difference(P <0.05);the expression level of histone in aerobic ginger group increased,but with no significant difference(P > 0.05);Compared with model group,the histone expression levels of curcumin in aerobic group and curcumin group decreased significantly(P <0.05).The histone expression level of aerobic ginger decreased significantly(P <0.01).Compared with aerobic group,the histone expression level of aerobic ginger was decreased,and there was a significant difference(P < 0.05).Compared with curcumin group,the histone expression level of aerobic ginger supplementation decreased significantly(P < 0.05).(2)Caspase-12: Compared with blank group,the expression levels of histone increased in model group and aerobic group(P < 0.01),and the expression levels of histone increased in curcumin group and aerobic plus ginger group(P < 0.05);Compared with model group,the histone expression levels of aerobic group,curcumin group and aerobic plus ginger group decreased significantly(P < 0.01).Compared with aerobic group and curcumin group,the histone expression level of aerobic ginger was decreased with significant difference(P < 0.05).(3)CHOP: Compared with blank group,the expression levels of histone increased in model group and aerobic group(P < 0.01),while the expression levels of histone increased in curcumin group and aerobic plus ginger group(P < 0.05);Compared with model group,the histone expression levels of aerobic group,curcumin group and aerobic plus ginger group decreased significantly(P < 0.01).Compared with aerobic group and curcumin group,the histone expression level of aerobic ginger was decreased with significant difference(P < 0.05).4.Conclusions:4.1 Aerobic exercise and curcumin drug intervention increased the body weight of rats,decreased the contents of FBG,TC,TG,LDL and FINS in serum,and increased the contents of HDL.The results showed that aerobic exercise,curcumin medicine and aerobic exercise combined with curcumin could improve the weight loss,glucose and lipid metabolism disorder and serum insulin decline in T2 DM rats with NAFLD,and the best intervention effect was aerobic exercise combined with curcumin.4.2 Aerobic exercise and curcumin drug intervention reduced liver index,serum AST and ALT contents and the number of lipid droplets in liver of rats.These results indicated that aerobic exercise,curcumin medicine and aerobic exercise combined with curcumin could improve liver index,liver function and hepatocyte steatosis in T2 DM rats with NAFLD,and aerobic exercise combined with curcumin had the best effect without increasing the burden of liver.4.3 Aerobic exercise and curcumin drug intervention reduced the expression levels of GRP78,CHOP and Caspase-12 in the liver of rats.The results showed that aerobic exercise,curcumin medicine and aerobic exercise combined with curcumin could improve the stress of liver ER in T2 DM rats with NAFLD,and the best intervention effect was aerobic exercise combined with curcumin.