Effects And Differences On Renal Structure And Function Between Different GLP-1 Analogues In Diabetic Nephropathy Rats

BackgroundDiabetic nephropathy(DN)is one of the most common microvascular complications of type 2 diabetes.30% to 40% of diabetic patients are associated with kidney damage and seriously affect the quality of life of patients,giving patients a huge financial burden.Glucagon-like peptide 1(GLP-1)analogues are a novel drug for clinical treatment of diabetes in recent years,through selecting high affinity receptor(GLP-1R)binding,play a role in promoting insulin secretion,reduce glucagon secretion,delay gastric emptying,enhance satiety,inhibit appetite,increase liver glycogen synthesis,reduce liver glycogen breakdown and other aspects of hypoglycemic effect.GLP-1Rs are widely found in the kidney,heart,liver and other vital organs of the body.In recent years,a large number of studies have shown that GLP-1 analogues can reduce the inflammatory response,inhibit oxidative stress,improve advanced glycogen end products(AGEs)and other aspects of the pathogenesis of DN outside the kidney protection.Currently in China listed GLP-1analogues are exenatide(exenatide)and liraglutide(liraglutide).Liraglutide and exenatide are available through the combination with GLP-1R delay the development of DN,however,both synthetic origin,metabolic pathways are not the same,the efficacy of two drugs used in the DN patients is unclear whether there are differences.ObjectiveExplore the mechanism of the GLP-1 analogue treatment DN;is there a difference in the protective effect of A and exenatide on renal structure and function during DN onset.MethodsFifty male SD rats were randomly divided into normal control group(10 rats),another 40 rats high-sugar and high-fat diet 6 weeks induced insulin resistance,then injection of a small dose of streptozotocin(STZ)by intraperitoneal destruction of pancreatic ? cells,the formation of type 2 diabetes characterized in insulin resistance and lack of insulin secretion.On the 3rd day and the 7th day,the fasting veins blood glucose was measured,and both the blood glucose was?16.7 mmol/L confirm the truth of DN model.Select 30 molded rats were randomly divided into 32 model group(10 rats),liraglutide treatment group(11 rats)and exenatide treatment group(11 rats).The normal control group and the model group were given subcutaneous injection of saline(10?L/Kg/12h);the exenatide treatment group was given subcutaneous injection of exenatide(10 ?L/Kg/12h);the liraglutide treatment group was given subcutaneous injection of liraglutide(0.3 mg/Kg/12h),continuous medication for 8 weeks.At the end of the 8th week,blood samples and kidney specimens were collected.Serum were collected after centrifugation blood samples,then the serum using automatic biochemical analyzer to detect rat blood urea nitrogen(BUN)and serum creatinine(Scr);kidney specimens were made into wax pieces,and the changes of renal tissue structure were observed by hematoxylin and eosin stain(HE)and Periodic Acid-Schiff stain(PAS);immunohistochemistry was used to observe the expression of transforming growth factor-?1(TGF-?1)and nicotinamide adenine dinucleotide phosphate oxidase 4(NOX 4)protein in the kidney tissues of rats and Semi-quantitative analysis of TGF-?1 and NOX 4protein levels in renal tissue was performed using Image-pro Plus software,real-time fluorescent quantitative PCR(RT-qPCR)was used to detect the mRNA expression of TGF-?1 and NOX 4 in renal tissues.SPSS19.0 software was used for statistical analysis,the results of measurement data were expressed as mean � standard deviation.A single factor analysis of variance between the two groups.The t test was used to compare the two groups.The test level was ? = 0.05.ResultsCompared with the normal control group,the levels of fasting blood glucose,BUN,Scr and TGF-?1 and NOX 4 protein levels in renal tissue were significantly increased in model group and exenatide treatment group(P<0.05);the levels of fasting blood glucose and TGF-?1 protein levels in renal tissue of liraglutide treatment group were significantly higher than those in normal control group(P<0.05);the body weight of the rats in the model group,liraglutide treatment group and the exenatide treatment group were significantly decreased(P<0.05),the morphology of the renal tissue showed thickening of the glomerular mesangium,The thickening of the model group was most pronounced and the liraglutide treatment group was the lightest.Compared with the model group,the levels of BUN,Scr in liraglutide treatment group and exenatide treatment group were significantly decreased(P<0.05),the levels of TGF-?1 and NOX 4 protein and mRNA levels in renal tissue in liraglutide treatment group were significantly decreased(P<0.05),and TGF-?1 and NOX 4 protein and TGF-?1 mRNA levels in renal tissue exenatide treatment group were significantly decreased(P<0.05).The level of Scr and TGF-?1 and NOX 4 protein levels and mRNA levels in renal tissue of liraglutide treatment group was significantly lower than that of exenatide treatment group(P<0.05).Conclusions1.GLP-1 analogue liraglutide and exenatide can decrease the expression of TGF-?1and NOX 4 protein and mRNA levels in renal tissue,the levels of BUN and Scr in DN rats and delay the development of diabetic nephropathy.2.Short-term application of liraglutide and exenatide treatment of DN,liraglutide reduced compared with exenatide to better model of rat kidney tissue TGF-?1,NOX 4protein and mRNA levels,to achieve lower BUN,Scr level.