Effects Of Duodenal-jejunal Bypass On Diabetic Renal Lesion And MMP-2/TIMP-2 Expression In T2DM Rats

Objective:Duodenal-jejunal bypass (DJB) has been proved to be an effective surgical treatment to control T2DM with or without obesity. Aberrant expression and activity of MMPs and TIMPs were implied in the development of diabetic nephropathy. We aimed to investigate the therapeutic effect of DJB on diabetic nephropathy, and to explorer whether the effect is MMPs/TIMPs related.Methods:A T2DM rat model was established by high fat diet feeding and streptozotocin injection. All SD rats were divided into 3 groups:ctr (n=9), T2DM+sham DJB (n=9) and T2DM+DJB (n=9). Clinical and metabolic parameters were monitored periodically. Expressions of MMP-2, MMP-9, TIMP-1 and TIMP-2 were characterized by immunohistochemistry. Gelatin zymography was applied to determine the activity of MMPs.Results:DJB intervention significantly improved insulin sensitivity and glucose tolerance, prevented the deterioration of renal function as shown by improvement of 24h urine volume, total urine protein, and BUN. Furthermore, DJB intervention regained the expression balance of MMP-2 and TIMP-2 and increased the activity of MMP-2 which was suppressed in T2DM.Conclusions:Our data suggested that DJB can effectively prevent the progression of renal function in diabetic nephropathy, and reversion of renal function in T2DM may be related to MMP-2 modulated ECM degradation.