Expression Of Klotho Gene In Diabetic Nephropathy Mouse Model And The Interference Effect Of Shen’an Granular

Diabetic nephropathy is the glomerular sclerosis caused by abnormal metabolism of diabetic,which is the most common cause of end-stage renal disease at home and abroad.The metabolic disorders is very complex in patients of diabetic nephropathy, once developed to end-stage renal disease,treatments are often more difficult than other kidney diseases.So,explore its pathogenesis to developing more effective preventions and control measures and finding new drugs,which has become the subject of educational circles of diabetes and nephrology and pharmacy extremely urgent. ObjectiveTo establish a DN mouse model, detect blood biochemical cha nges and explore the expression of KL gene in DN mouse model an d the interference effect of Shen’an Granular Methods62 C57BL/7 mice were randomly divided into normal rats group(A group,n=12),model group(B group,n=12),losartan group(C group,n=13),Shen’an Granular of low dose group(D group,n=13),Shen’an Granular of high dose group(E group,n=13).Diabet-ic nephropathy model was induced by a single intraperitoneal streptozotocin solution(150 mg/kg) injection.After 8 weeks of treatment with drugs,we tested the urine and blood biochemistry before and after treatment.The left kidney was used for light and electron microscopic s-ections;The right kidney was storaged in the-70℃ refrigera-tor,renal KL m RNA detected by RT-P CR;renal KL protein,Wnt1 pr-otein, β-catenin protein,nephrin protein and E-cadherin protein detected by Western blot method. ResultsDuring the treatment period, 4 mice died,there were 58 mice survival in all at last.Before treatment:compared with A group,urine and blood biochemical results in the B,C,D,E groups were significantly higher(P<0.05);between B,C,D and E group(P>0.05).After treatment:compared with before treatment,there was no significant difference in urine and blood biochemical results of A group(P>0.05);urine and blood biochemical results in the B group were significantly higher(P<0.05);urine biochemical re-s ults,BUN,Scr,CHOL,TG results in the C,D and E groups were sig-n ificantly higher(P<0.05);but there was no significant differ-en ce in TP and ALB results(P>0.05).Renal pathology:The kidney structure of group A was normal.Compared with group A,glomerular hypertrophy, glomerular basement membrane thicken,Mesangial matrix and Mesangial cells proliferation,Podocyte foot process fusion,even fall off and fibrosis were obvious.After treatment,renal pathological structure were much better than B group.Renal KL m RNA and KL protein of every groups:compared with A group,the expression of KL m RNA and KL protein in group B,C,D and E were obviously decreased(P<0.05);compared with B group,the expression of KL m RNA and KL protein in group C,D and E were dramatically increased(P<0.05);there was no significant d-i fference in the expression of KL m RNA and KL protein between C and E group,but was higher than D group(P<0.05). the expressi-o n of Wnt1 protein and β-catenin protein:compared with group A,group B,C,D and E were obviously increased(P<0.05);compared with group B,group C,D and E were obviously decreased(P<0.05); there was no significant difference between C and E group,but was lower than D group(P<0.05). the expression of nephrin protein:compared with A group,group B,C,D and E were obviously decreased(P<0.05);compared with B group,group C,D and E were dramatically increased(P<0.05);there was no significant differe-n ce between C and D group,but was lower than E group(P<0.05). The expression of E-cadherin protein:compared with A group,group B,C,D and E were obviously decreased(P<0.05);compared with B group,group C,D and E were dramatically increased(P<0.05); there was no significant difference between C and E group,but was lower than D group(P<0.05). Conclusions1.Intraperitoneal injection of STZ solution(150mg/kg) can succeed induced diabetic nephropathy mouse model.2.Shen’an Granular has the functions of improving renal function,reducing proteinuria and correcting the disorder of lipid metabolism.3.The diabetic nephropathy mouse could lead to proteinuria,renal function impaired and the lipid metabolism disordered.4.The expression of KL gene in DN mouse model suppressed,t-helow Klotho gene is closely related to Wnt1 protein and β-cat enin protein,Shen’an granular can produce favorable effects in the high expression of Klotho gene and osteoblast factor in the wnt/β-catenin signaling pathway,and inhibite podocyte epithelial mesenchymal transdifferentiation,so as to ptotecting podocyte,reducing proteinuria and glomerular sclerosis,slowing down the pace of Diabetic nephropathy.