| Objective:To evaluate the effects and mechanism of Dangua prescription on glycolipid metabolism and the expressions of adiponectin/AMP-activated protein kinase/peroxisome profierator-acyivated receptor y(APN/AMPKa/PPAR-y)signal transduction pathway in streptozotocin induced diabetic rats.To assess the partly mechanism of glycolipid metabolism by Dangua prescription.Method:After one-week adaptive feeding,4 rats were removed,60 male Sprague Dawley rats were randomly divided into normal group(control,n=10,fed with normal diet)and model established group(n=50).Diabetic rats were induced by intraperitoneal injection of Streptozoein(STZ,25 mg/(kg·d),interval 2 days)after high-fat and high-sugar diet for 4 weeks.After the modeling,rats measured twice in fasting blood glucose ?11.1 mmol/L were randomly divided into 4 groups:model group,metformin group(MFG),medium dose Dangua prescription group(MDG)and high dose Dangua prescription group(HDG),they were intervened by corresponding drugs.After 16-weeks intervention,the basic indicators of glycolipid metabolism,including fasting plasma glucose(FPG),glycosylated hemoglobin Alc(HbAlc),triglyceride(TG),total cholesterol(TC)were detected,the liver function were measured by alanine aminotransferase(ALT)and aspartate aminotransferase(AST),the changes of pancreas tissue were observed by hematoxylin-eosin staining and electron microscopy,and the changes of livers tissue were observed by red O fat dyeing.The fasting Insulin(FINS),C-Peptide(C-P),Hydroxy methylglutaryl-CoA reductase(HMGR),glucose transporters4(GLUT4)were measured by Enzyme-Linked ImmunoSorbent Assay(ELISA).The expression levers of APN,AMPKa,PPAR-? mRNd proteins were measured by using Real-time PCR and West-blot.Results:1.The basic conditions of each group:;After 16-weeks intervention,compared with the model group,the conditions of MFG,MDG,HDG group was fine,such as the activities,colour of their hair,intake of food and water,weight,the output of stool and urine,mental.Besides,the weight of these rats were slightly decreased than before.2.The fasting glucose(FPG)and glycosylated hemoglobin Alc(HbAlc):Compared with the control group,the FPG of model group,MFG,MDG,HDG were significantly increased and was statistically significant(P<0.01),there was no difference between these groups.After intervention,compared with the model group,the FPG of MFG,MDG,HDG were significantly decreased(P<0.01)and the levels of HbAlc was decreased(P<0.05).3.The levels of triglyceride(TG)and total cholesterol(TC):After intervention,compared with the model group,the levels of TG and TC of MFG,MDG,HDG were significantly decreased(P<0.05).4.The levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST):After intervention,compared with the model group,the levels of AST and ALT of MFG,MDG,HDG were significantly decreased(P<0.01);Compared with the MFG,the levels of ALT of MDG,HDG were decreased(P<0.05).5.The levels of fasting Insulin(FINS)and C-Peptide(C-P):After intervention,compared with the control group,the levels of FINS and C-P of model group were significantly increased(P<0.01);Compared with the model group,the levels of FINS and C-P of MFG,MDG,HDG were decreased(P<0.05),there was no difference between these groups.6.The levels of glucose transporters 4(GLUT4)and Hydroxy methylglutaryl-CoA reductase(HMGR):After intervention,compared with the model group,the levels of GLUT4 of MFG,MDG,HDG were significantly increased(P<0.01),while the levels of HMGR were decreased(P<0.05).7.The hematoxylin-eosin staining and electron microscopy of pancreas tissue:The hematoxylin-eosin staining of pancreas tissue showed that the pancreas islet number,islet morphology,islet distribution,islet secretory granules in model group,MFG,MDG,HDG were damaged to some degree.The electron microscopy of pancreas tissue showed that the tucleus size,nuclear membrane morphology,secretory granules,mitochondria,mitochondrial cristae,and rough endoplasmic reticulum in model group,MFG,MDG,HDG were also damaged.Compared with the model group,each intervention group had a certain repair effect on the damaged pancreatic tissue in the microcellular organelles and macroscopic cell morphology.8.The red O fat dyeing livers tissue:Compared with the control group,the lipid droplets of model group,MFG,MDG,HDG were significantly increased.There were messy lipid droplets in model group,the MFG was less than model group,the lipid droplets of MDG were least.9.Real-time PCR:Compared with the model group,the expression levers of APN,AMPKa,PPAR-y mRNA in MFG,MDG,HDG were significantly increased(P<0.05),and there was no difference between these groups.Compared with the MDG,the expression levers of AMPK-? were significantly increased(P<0.05).10.West-blot:Compared with the model group,the expression levers of APN,AMPK?,P-AMPK?,PPAR-? proteins in MFG were significantly increased(P<0.05).Compared with the MFG,the expression levers of P-AMPK? proteins in MDG and HDG were significantly increased(P<0.05),while there was no difference in the expression levers of APN,AMPK?,PPAR-? protein.Compared with the MDG,the expression levers of AMPK?,P-AMPK? proteins in MFG were significantly increased(P<0.05),while there was no difference in the expression levers of APN,PPAR-? protein.Conclusion:1.Dangua prescription showed positive effect on glycolipid metabolism in diabetic rats.2.Dangua prescription had a certain repair effect on liver injury,pancreas structure and hepatic lipid droplet degeneration.3.Dangua prescription could improve glycolipid metabolism in diabetic rats may be associated with the activation of APN/AMPK/PPAR-y signal pathway. |
PDF Full Text Request