| Purpose:Objective to investigate the occurrence and development of type 2 diabetic nephropathy and the intervention of aerobic exercise and its relationship with TGF-beta 1-Notch1 signaling pathway.Method:30 rats from the 80 week old SD rats were taken as control group(NC group,n=30).The rats were fed with high fat diet on the basis of intraperitoneal injection of STZ to replicate the model of type 2 diabetic rats.After successful modeling,the patients were randomly divided into diabetic control group(DMC,n=32)and diabetic exercise group(DME,n=21).The exercise group carried out 60min no load swimming training every day.Then in 0 weeks,2 weeks and 8 weeks after the observation of ultrastructure of rat kidney tissue,detection of FBG,INS,TC,TG,BUN,CREA in serum,content of Elisa in renal tissues of rats and detect the contents of ALB in urine of rats in Notch 1,Jagged 1,NICD1,HES1,TGF-beta 1 by testing,the renal tissues of rats in RT-PCR,JaggedlmRNA,HES1mRNA,Notch1mRNA change TGF-beta 1 mRNA expression.Result:(1)After the success of the model,the FBG and HOMA-IR of the DMC group increased significantly and then decreased significantly with the prolongation of time,and were significantly higher than those in the NC group at the end of the 0 week,the first week and the 8 week.Although there was no significant difference in serum INS level.The FBG content in group DME was significantly lower than that in group DMC after 2 and 8 weeks.(2)Compared with NC group,serum TG and TC levels were significantly increased in the DMC group(P<0.05)at the end of the 0 week.After 2 weeks of experiment,the serum TG and TC in the DMC group were significantly higher than those in the NC group(P<0.01),but the TG content of the DME group was significantly lower than that of group DMC(P<0.05).After 8 weeks of experiment,DMC group of serum TG and TC were significantly higher than that of NC group(P<0.05),while in DME group,serum TG content was significantly lower than that of group DMC(P<0.05),while DME serum TC was lower than group DMC,but no significant difference.A comparison between 0,2 and 8 weeks showed a significant increase in serum TG and TC levels in the DMC group at week 2 and week 0(P<0.05).Compared with 2 weeks,the serum TG and TC levels in group DMC and group DME were decreased,but there was no significant difference between the 8 groups.(3)After the successful modeling of DM rats for the first time in 8 weeks,under the electron microscope,the glomerular capillary basement membrane in DMC group was homogeneous,the structure was not clear,the matrix of the system was increased,and the foot process was widened or widely fused.The urine ALB content in DMC group was significantly higher than that in group NC(P<0.01).In the DME group,the ultrastructure of renal tissue was significantly improved and the glomerular basement membrane thickness was significantly reduced,and the urinary ALB content in the DME group was significantly lower than that in the DMC group(P<0.01).(4)In 0 weeks,compared with group NC,renal tissue in the DMC group TGF-beta 1 protein content and mRNA expression significantly increased(P<0.01),increased Notch 1 and HES1 content,but no significant difference(P>0.05),Notch1mRNA and HES1mRNA expression was significantly increased(P<0.05 P<0.01).After 2 weeks of experiment,the renal tissue in the DMC group TGF-beta 1,Notch 1 protein content and mRNA expression compared with NC group significantly increased(P<0.01),the content of HES1 and mRNA expression compared with the NC group were significantly increased(P<0.05,P<0.01),renal tissue in the DME group TGF-the content of beta 1 and mRNA expression compared with NC group significantly increased(P<0.01),Notch1mRNA and HES1mRNA expression compared with NC group were significantly increased(P<0.01),compared with the DMC group,DME group TGF-beta 1,HES1 content and the expression of mRNA is relatively small,but the differences were not significant(P>0.05),the content of Notch1 decreased,but no significant difference(P>0.05),significantly reduced the expression of Notch1mRNA(P<0.05).But after 8 weeks of experiment,DMC group TGF-beta 1,Notchl,HES1 protein and mRNA expression compared with NC group significantly increased(P<0.01),renal tissue in the DME group TGF-beta 1,HES1 protein content and the expression of mRNA and NC groups have no significant difference(P>0.05),kidney in the expression of NotchlmRNA was compared with NC group were significantly increased(P<0.05),while the DME group TGF-beta 1,Notchl protein content and mRNA expression compared with DMC group significantly decreased(P<0.01),the content of HES1 compared with the DMC group,was significantly reduced(P<0.05),HES1mRNA the relative expression of less than DMC group,but no significant difference(P>0.05).Seen from the comparison between the 0 and 2 weeks and 8 weeks,compared with 0 weeks,2 weeks of DMC group TGF-beta 1 protein content and mRNA expression significantly increased(P<0.01),DMC group TGF-beta ImRNA expression 8 weeks significantly increased(P<0.01),was significantly the increase of Notch 1 content and the expression of mRNA in 2 and 8 weeks in group DMC in renal tissues(P<0.05.P<0.01).Compared with 2 weeks,TGF-and mRNA expression in DMC group and DME group were significantly different between the group and the group(P<0.05).There was no significant difference in the expression of Notchl,Hesl and mRNA between the DMC group and DME group(P>0.05)Conclusion:(1)The model of rats with type 2 diabetes in this study was successful.(2)With the progression of diabetes,hyperglycemia and dyslipidemia,through a variety of ways leads to increased expression of TGF-beta 1,Notch1 signal pathway induced podocyte injury,promote the occurrence and development of DN,decrease the proteinuria and renal function.(3)Long term aerobic exercise can significantly improve the diabetic rats,glucose and lipid metabolism,control of renal tissue TGF-beta 1 expression and down-regulation of Notch1 signaling pathway,so as to effectively prevent the occurrence and development of type 2 diabetic nephropathy,reduce urinary albumin excretion,protect kidney function. |
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