Protective Effect of Roux-en-Y Gastric Bypass Surgery on Early Damage of Renal Tissue in Type 2 Diabetes Mellitus Rats_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 WENYi ¹ , QIQiao ² , LIUDan-qiang ¹ , HUANGShang-qing ¹ , LINNing ¹ , SHILi ¹ , CHENTao ¹ ,  TANGLi-jun ¹

1. Department of General Surgery, Chengdu Military General Hospital, Chengdu 610083, Sichuan Province, China;
2. The Outpatient Department, 95879 Unit, Chengdu 610083, Sichuan Province, China;

Corresponding author：

TANGLi-jun, Email: 13258198900@163.com

Keywords：

Gastric bypass surgery; Diabetic nephropathy; Transforming growth factor; Nicotinamide adenine dinucleotide phosphate oxidase; Intercellular adhesion molecule; Bcl-2 protein

DOI：

10.7507/1007-9424.20150109

Video：

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Objective To investigate the protective effect of Roux-en-Y gastric bypass surgery on early damage of renal tissue in type 2 diabetes mellitus rats, and explore the mechanism of the protective effects. Methods Diabetes mellitus animal models were induced by intraperitoneal injection of streptozotocin (STZ, 35 mg /kg) and a high-fat diet.Diabetic rats were divided into three groups randomly (digital table method): diabetes control group (n=8), sham operation group (n=8), and Roux-en-Y gastric bypass group (n=14).Another 8 normal SD rats as the normal control group.The fasting blood glucose, serum total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA) were measured before operation and in 8 weeks after operation; plasma BUN and Cr were measured respectively before operation and in 4 and 8 weeks after operation in each group rats, 24 h urine microalbumin and urine 8-hydroxydeoxyguanosine were measured respectively before operation and in 8 weeks after operation in each group rats.Renal pathological changes were observed and the indexes of kidney hypertrophy, the mean glomerular area (MGA), and the mean glomerular volume (MGV) were analyzed in 8 weeks after operation.The expressions of fibronectin, typeⅣcollagen (CoⅣ), transforming growth factor-β1 (TGF-β1), intercellular adhesion molecule-1(ICAM-1), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), and Bcl-2 protein in renal tissues were investigated by immunohistochemical staining. Results Roux-en-Y gastric bypass surgery could reduce the blood glucose, blood lipid, MGA, MGV, and the index of kidney hypertrophy of diabetic rats significantly (P < 0.05), improved renal pathological morphology and kidney function (P < 0.05), reduced the protein expressions of fibronectin and CoⅣ, decreased the protein expressions of TGF-β1, ICAM-1, and NOX4, and increased the protein expression of Bcl-2. Conclusion Roux-en-Y gastric bypass surgery can improve kidney function and the pathological damage of diabetes rats, its mechanism may be related to inhibition the protein expressions of TGF-β1, ICAM-1, and NOX4, and increase the protein expression of Bcl-2.

Citation： WENYi, QIQiao, LIUDan-qiang, HUANGShang-qing, LINNing, SHILi, CHENTao, TANGLi-jun. Protective Effect of Roux-en-Y Gastric Bypass Surgery on Early Damage of Renal Tissue in Type 2 Diabetes Mellitus Rats. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(4): 404-411. doi: 10.7507/1007-9424.20150109 Copy

1.	Yan, HT, Tang LJ, Chen T, et al.Defining and predicting complete remission of type 2 diabetes:a short-term efficacy study of open gastric bypass.Obesity Facts, 2013, 6(2):176-184.
2.	Agrawal V, Khan I, Rai B, et al.The effect of weight loss after bariatric surgery on albuminuria.Clin Nephrol, 2008, 70(3):194-202.
3.	Saliba J, Kasim NR, Tamboli RA, et al.Roux-en-Y gastric bypass reverses renal glomerular but not tubular abnormalities in excessively obese diabetics.Surgery, 2010, 147(2):282-287.
4.	Srinivasan K, Viswanad B, Asrat L, et al.Combination of high-fat diet-fed and low-dose streptozotocin-treated rat:a model for type 2 diabetes and pharmacological screening.Pharmacol Res, 2005, 52(4):313-320.
5.	文敏, 周波, 余资江.免疫组织化学图像光度学参数的选择及测量.局解手术学杂志, 2009, 18(6):377-378.
6.	Magee GM, Bilous RW, Cardwell CR, et al.Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis.Diabetologia, 2009, 52(4):691-697.
7.	廉永昕, 张嘉莉, 李兢.糖尿病肾病发病机制研究进展.中国疗养医学, 2012, 12(6):515-516.
8.	Fowler SM, Kon V, Ma L, et al.Obesity-related focal and segmental glomerulosclerosis:normalization of proteinuria in an adolescent after bariatric surgery.Pediatr Nephrol, 2009, 24(4):851-855.
9.	Alexander JW, Goodman HR, Hawver LR, et al.Improvement and stabilization of chronic kidney disease after gastric bypass.Surg Obes Relat Dis, 2009, 5(2):237-241.
10.	Lan HY.Diverse roles of TGF-β/Smads in renal fibrosis and inflam-mation.Int J Biol Sci, 2011, 7(7):1056-1067.
11.	Sotkes MB, Holler S, Cui Y, et al.Expression of decorin, biglyein, and collgane typeⅠin human renal fibrosis disease.Kidney Int, 2000, 57(2):487-498.
12.	Petersen M, Thorikay M, Deckers M, et al.Oral administration of GW788388, an inhibitor of TGF-beta typeⅠandⅡreceptor kinases, decreases renal fibrosis.Kidney Int, 2008, 73(6):705-715.
13.	Valladares-Salgado A, Angeles-Martlnez J, Rosas M, et al.Association of polymorphisms within the transforming growth factor-β1 with diabetic nephmpathy and serum cholesterol and triglyceride concentrations.Nephrology, 2010, 15(6):644-648.
14.	Shiose A, Kuroda J, Tsuruya K, et al.A novel superoxide-producing NAD(P)H oxidase in kidney.J Biol Chem, 2001, 276(2):1417-1423.
15.	Gorin Y, Block K, Hernandez J, et al.Nox4 NAD(P)H oxidase mediates hypertrophy and fibronectin expression in the diabetic kidney.J Biol Chem, 2005, 280(47):39616-39626.
16.	Sharma K, Ramachandrarao S, Qiu G, et al.Adiponectin regulates albuminuria and podocyte function in mice.J Clin Invest, 2008, 118(5):1645-1656.
17.	Etoh T, Inoguchi T, Kakimoto M, et al.Increased expression of NAD(P)H oxidase subunits, NOX4 and p22phox, in the kidney of streptozotocin-induced diabetic rats and its reversibity by interventive insulin treatment.Diabetologia, 2003, 46(10):1428-1437.
18.	Liu G, Sun Y, Li Z, et al.Apoptosis induced by endoplasmic reticulum stress involved in diabetic kidney disease.Biochem Biophys Res Commun, 2008, 370(4):651-656.
19.	Reed JC, Zha H, Aime-Sempe C, et al.Structure-function analysis of Bcl-2 family proteins.Regulators of programmed cell death.Adv Exp Med Biol, 1996, 406:99-112.
20.	Ortiz A, Ziyadeh FN, Neilson EG.Expression of apoptosis-regulatory genes in renal proximal tubular epith elial cells exposed to high ambient glucose and in diabetic kidneys.J Investig Med, 1997, 45(2):50-56.
21.	Dal Canton A, Fuiano G, Sepe V, et al.Mesangial expression of intercellular adhesion molecule-1 in primary glomerulosclerosis.Kidney Int, 1992, 41(4):951-955.
22.	Sugimoto H, Shikata K, Hirata K, et al.Increased expression of intercellular adhesion molecule-1 (ICAM-1) in diabetic rat glomeruli:glomerular hyperfiltration is a potential mechanism of ICAM-1 upregulation.Diabetes, 1997, 46(12):2075-2081.

1. Yan, HT, Tang LJ, Chen T, et al.Defining and predicting complete remission of type 2 diabetes:a short-term efficacy study of open gastric bypass.Obesity Facts, 2013, 6(2):176-184.
2. Agrawal V, Khan I, Rai B, et al.The effect of weight loss after bariatric surgery on albuminuria.Clin Nephrol, 2008, 70(3):194-202.
3. Saliba J, Kasim NR, Tamboli RA, et al.Roux-en-Y gastric bypass reverses renal glomerular but not tubular abnormalities in excessively obese diabetics.Surgery, 2010, 147(2):282-287.
4. Srinivasan K, Viswanad B, Asrat L, et al.Combination of high-fat diet-fed and low-dose streptozotocin-treated rat:a model for type 2 diabetes and pharmacological screening.Pharmacol Res, 2005, 52(4):313-320.
5. 文敏, 周波, 余资江.免疫组织化学图像光度学参数的选择及测量.局解手术学杂志, 2009, 18(6):377-378.
6. Magee GM, Bilous RW, Cardwell CR, et al.Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis.Diabetologia, 2009, 52(4):691-697.
7. 廉永昕, 张嘉莉, 李兢.糖尿病肾病发病机制研究进展.中国疗养医学, 2012, 12(6):515-516.
8. Fowler SM, Kon V, Ma L, et al.Obesity-related focal and segmental glomerulosclerosis:normalization of proteinuria in an adolescent after bariatric surgery.Pediatr Nephrol, 2009, 24(4):851-855.
9. Alexander JW, Goodman HR, Hawver LR, et al.Improvement and stabilization of chronic kidney disease after gastric bypass.Surg Obes Relat Dis, 2009, 5(2):237-241.
10. Lan HY.Diverse roles of TGF-β/Smads in renal fibrosis and inflam-mation.Int J Biol Sci, 2011, 7(7):1056-1067.
11. Sotkes MB, Holler S, Cui Y, et al.Expression of decorin, biglyein, and collgane typeⅠin human renal fibrosis disease.Kidney Int, 2000, 57(2):487-498.
12. Petersen M, Thorikay M, Deckers M, et al.Oral administration of GW788388, an inhibitor of TGF-beta typeⅠandⅡreceptor kinases, decreases renal fibrosis.Kidney Int, 2008, 73(6):705-715.
13. Valladares-Salgado A, Angeles-Martlnez J, Rosas M, et al.Association of polymorphisms within the transforming growth factor-β1 with diabetic nephmpathy and serum cholesterol and triglyceride concentrations.Nephrology, 2010, 15(6):644-648.
14. Shiose A, Kuroda J, Tsuruya K, et al.A novel superoxide-producing NAD(P)H oxidase in kidney.J Biol Chem, 2001, 276(2):1417-1423.
15. Gorin Y, Block K, Hernandez J, et al.Nox4 NAD(P)H oxidase mediates hypertrophy and fibronectin expression in the diabetic kidney.J Biol Chem, 2005, 280(47):39616-39626.
16. Sharma K, Ramachandrarao S, Qiu G, et al.Adiponectin regulates albuminuria and podocyte function in mice.J Clin Invest, 2008, 118(5):1645-1656.
17. Etoh T, Inoguchi T, Kakimoto M, et al.Increased expression of NAD(P)H oxidase subunits, NOX4 and p22phox, in the kidney of streptozotocin-induced diabetic rats and its reversibity by interventive insulin treatment.Diabetologia, 2003, 46(10):1428-1437.
18. Liu G, Sun Y, Li Z, et al.Apoptosis induced by endoplasmic reticulum stress involved in diabetic kidney disease.Biochem Biophys Res Commun, 2008, 370(4):651-656.
19. Reed JC, Zha H, Aime-Sempe C, et al.Structure-function analysis of Bcl-2 family proteins.Regulators of programmed cell death.Adv Exp Med Biol, 1996, 406:99-112.
20. Ortiz A, Ziyadeh FN, Neilson EG.Expression of apoptosis-regulatory genes in renal proximal tubular epith elial cells exposed to high ambient glucose and in diabetic kidneys.J Investig Med, 1997, 45(2):50-56.
21. Dal Canton A, Fuiano G, Sepe V, et al.Mesangial expression of intercellular adhesion molecule-1 in primary glomerulosclerosis.Kidney Int, 1992, 41(4):951-955.
22. Sugimoto H, Shikata K, Hirata K, et al.Increased expression of intercellular adhesion molecule-1 (ICAM-1) in diabetic rat glomeruli:glomerular hyperfiltration is a potential mechanism of ICAM-1 upregulation.Diabetes, 1997, 46(12):2075-2081.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Protective Effect of Roux-en-Y Gastric Bypass Surgery on Early Damage of Renal Tissue in Type 2 Diabetes Mellitus Rats

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