The Effect Of Astragalus Liuyi Decotion On Glucose Reabsorption Of The Renal Tubular Epithelium Regulated

ObjectiveThe study was to investigate the therapeutic effect of Yiqi Jianpi Recipe Astragalus Liuyi Decoction on Diabetic Model Rats,and to explore the possible mechanism of the effect of glucose uptake affect by SGLT2/GLUT2-mediated renal tubular epithelial,provide a new method for the prevention and treatment of diabetes,and provide a scientific basis for the discussion of Astragalus Liu Yi Decoction in diabetes.Methods1.Fed the streptozotocin-induced rats with high fat and high glucose food.The effect of intraperitoneal injection of four different doses of STZ was observed at 25mg/kg,30mg/kg,35mg/kg and 40mg/kg respectively according to the histopathological observation of pancreas and kidney,general condition,fasting blood glucose,glycosylated hemoglobin.Selected the most appropriate STZ intraperitoneal injection dose,and know the development process of diabetes model and lay the foundation for the follow-up study.2.Copy the model of type 2 diabetes mellitus,treated with Astragalus Liuyi Decoction at 3.15g/kg,6.30g/kg and 12.60g/kg and the compare group with Dapagliflozin at 0.5mg/kg,observe the levels of body weight,food intake,fasting blood glucose,and after 6 weeks of administration,blood samples were taken to detect glycosylated hemoglobin,blood lipid,plasma insulin,the histopathological examination of kidney and pancreas tissue and the renal tissue SGLT2,GLLUT2 protein expression and mRNA expression.3.Observed the effects of SGLT2 and GLUT2 protein on renal tubular epithelial cells by immunohistochemistry and western blot respectively.4.The expression of slc5a2 and slc2a2 genes in renal tissues of rats were observed by fluorescence quantitative PCR.5.This study was to investigate the therapeutic effect of Astragalus Liuyi Decoction and its possible mechanism by regulating the glucose reabsorption of renal tubular epithelial cells by SGLT2/GLUT2.Results1.through comparative study found that high-fat high-sugar feed for 4 weeks,30mg/kg body weight dose of rats given a one-time intraperitonealinjection of STZ,can build a similar to type 2 diabetes model,the modelis more stable.Fasting blood glucose>11.lmmol/L were seem as the success building,and the damage is relatively light.No animal death occurs within 6 weeks after intraperitoneal injection.The 30 mg/kg dose of STZ is suitable for the study.2.The model of type 2 diabetes mellitus was successfully built.The symptoms of the rats were significantly higher than those of the control group.The symptoms,blood glucose and glycosylated hemoglobin were significantly increased.The structure of pancreatic islets was clearly observed.The result of HE staining showed that the renal glomeruli,the collection of tubules,proximal tubules and distal tubules were completely intact and without obvious pathological damage.There was no significant change in plasma insulin levels in the model rat.The rats in the model group were treated with Astragalus Liuyi Decoction for 6 weeks,and the blood glucose and glycosylated blood red blood albumin were better than the model control group.The general symptoms of the spleen deficiency were also eased.There was no significant impact on blood lipids.3.The expression of SGLT2 and GLUT2 in the renal tubules of model rats were significantly higher than those of the control group(P<0.05).After 6 weeks treated with high fat and high glucose diet the expression of SGLT2 and GLUT2 in the rats increased.Western blot was used to detect the expression of SGLT2 and GLUT2 protein in renal tissue.The expression of SGLT2 in the kidney of the model group was increased and the expression of SGLT2 was decreased after treatment with Astragalus Liuyi Decotion.The expression of GLUT2 of the model group decreased but increased expression after the treatment of Astragalus Liuyi Decotion.4.The results of qPCR showed that the expression of slc5a2 in Dapagliflozin and Astragalus Liuyi Decoction group was also lower than that in the model group.ConclusionAstragalus Liuyi Decoction has a good therapeutic effect on experimental diabetic rats,which can reduce blood glucose and glycosylated hemoglobin in experimental diabetic rats.The expression of SGLT2 and GLUT2 in renal tissue of diabetic rats induced by high glucose and high fat diet combined with intraperitoneal injection of streptozotocin induced diabetic rats increased the expression of SGLT2 and GLUT2 in diabetic rats.The possible reason for the increased expression of SGLT2 and GLUT2 in diabetic rats was due to the increase of blood glucose,Glomerular filtration increased the amount of glucose,which in turn leads to an increase in the amount of glucose from the renal tubular epithelium.The results of this study show that Astragalus Liuyi Decotion has a certain regulatory in the SGLT2 protein expression of diabetic model.The hypoglycemic effect of Astragalus Liuyi Decoction may be through the regulation of SGLT2 in the part of renal tubular epithelial which for reabsorb glucose.