Effects of Roux-en-Y gastric bypass on the renal function of rats with type 2 diabetes mellitus

Objective To investigate the effects of Roux-en-Y gastric bypass on the renal function of rats with type 2 diabetes mellitus.Methods Rat models of type 2 diabetes mellitus were established by intraperitoneal injection of streptozotocin (35 μg/g) and a high-fat diet.All the rats were randomly divided into diabetes group (8 rats),sham operation group (8 rats) and Roux-en-Y gastric bypass group (14 rats).Another 8 normal rats were selected in the normal control group.The level of fasting blood glucose was detected preoperatively and 8 weeks after the operation.The levels of blood urea nitrogen and creatinine were detected preoperatively and 4 and 8 weeks after the operation.Pathological changes of the renal tissue were observed and the indexes of kidney hypertrophy were analyzed 8 weeks after the operation.The expressions of fibronectin,type Ⅳ collagen and TGF-β1 were detected by immunohistochemical staining.The mRNA and protein expressions of MMP-2 and MMP-9 were detected by Real-time PCR and Western blot,respectively.All data were analyzed using the analysis of variance or LSD test.Results In postoperative week 8,the levels of fasting glucose,blood urea nitrogen,creatinine and index of kidney hypertrophy were (15.9 ± 1.6) mmol/L,(9.2 ± 0.6) mmol/L,(44 ± 4) μmol/L and (10.7 ± 1.5)mg/g in the diabetes group,and (5.9 ±0.7) mmol/L,(6.6 ±0.4) mmol/L,(30 ±2) μmol/L and (8.6 ± 0.6)mg/g in the Roux-en-Y gastric bypass group,with significant difference between the 2 groups (P ＜ 0.05).Compared with the normal control group,the volumes of glomerulus of kidney in the diabetes group and the sham operation group were greater,and mesangial proliferation was detected.The integral optical density of fibronectin,type Ⅳ collagen,TGF-β1,the mRNA and protein expressions of MMP-2 and MMP-9 were 664 ± 23,86 ± 5,52 ± 6,1.00 ± 0.04,64 ± 4,1.00 ± 0.20,48 ± 5 in the normal control group,and 1665 ± 44,789 ±66,459 ±35,0.52 ±0.13,51 ±6,0.36 ±0.05,38 ±4 in the diabetes group,and 1701 ±55,754 ±49,425 ± 42,0.54 ± 0.19,48 ± 5,0.43 ± 0.09,39 ± 4 in the sham operation group,and 1105 ± 61,195 ± 11,147 ± 16,1.53 ±0.29,63 ±5,1.11 ±0.14,49 ±5 in the Roux-en-Y gastric bypass group,with significant difference between the 4 groups (F =1340.30,4982.50,2025.10,654.19,13.58,610.74,7.86,P ＜0.05).Significant difference was detected in pairwise comparison (P ＜ 0.05).Conclusion Roux-en-Y gastric bypass surgery can improve the renal function of rats with type 2 diabetes mellitus,reduce deposition of extracellular matrix.Its mechanism may be related to inhibition of TGF-β1 expression and increase of MMP-2 and MMP-9 mRNA and protein expressions. Key words: Diabetes mellitus, type 2;  Diabetic nephropathy;  Roux-en-Y gastric bypass