The Effect Of Curcumin On Diabetic Nephropathy In Db/db Mice

Background:Diabetic nephropathy is the most common complications of diabetes mellitus, which is the renal manifestations of idiopathic systemic microvascular disease in diabetes mellitus. Micro-albuminuria is considered to the main clinical manifestations in early of disease. The main Pathological changes of DN include capillary basement membrane thickening, mesangial matrix increased, eventually leading to glomerulosclerosis.The research confirmed that hyperglycemia is the initiating factor in several chronic complications of DM. Hyperglycemia mediates to oxidative stress, promotes to expression of cytokine factors and deposition of extracellular matrix proteins, contributes to the occurrence and development of diabetic nephropathy. Curcumin have anti-inflammatory, antioxidant, anti-atherosclerotic, anti-tumor and the protection of liver and kidney, and other pharmacological effects. So far, the domestic and international researches that the treatment of curcumin on DN were mostly STZ-induced rat model of DN. There is no report that curcumin treat the DN of type 2 DM in db/db mice. The purpose of this study is to testify the effect of curcumin on diabetic nephropathy in db/db mice of type 2 DM.Objective:To investigate the effect of curcumin on diabetic nephropathy in db/db mice of type 2 diabetes mellitus model.Methods:8 weeks female C57BLKS/J mice, including db/db mice 10, wild type mice 5.In 9 wk, three wild type mice and three db/db mice were chose randomly, the urine of 24 hours was collected, then tested microalbumin by ELISA in order to judge whether the model of DN is success. After the model of diabetic nephropathy succed,10 wk db/db mice and wild type mice were divided into three groups with five animals of each group. Normal control group, diabetic nephropathy group and diabetic nephropathy with curcumin. curcumin was administrated to diabetic mice at a dosage of 200 mg/(kg·d) for 18 successive weeks. At the end of study, the mice were sacrificed, body weight, kidney weight and serum creatinine and urea nitrogen was measured, kidney tissue was stained by PAS, detected expression of collagenⅣand Fibronectin in the kidney by immunohitochemistry staining.Results:In 9 wk, compared with normal mice, db/db mice display obviously much urine, drinking, eating and fat. The glucose and 24-hour urinary albumin excretion are significantly increased (P< 0.001). It shown that the model of diabetic nephropathy was success.At the end of study, the glucose and 24-hour urinary albumin excretion of db/db mice significantly higher than that of wild type mice (P<0.001), the serum urea nitrogen and creatinine increased slightly. Pathological examination revealed glomerular hypertrophy, mesangial expand, capillary basement membrane thickening of db/db mice. We found the expression of type IV collagen and FN increased in renal tissue by immunohistochemistry. Compared with model group, After 18 weeks of curcumin treatment in db/db mice, no significant changes in blood glucose and renal function,24-hour urinary albumin excretion was significantly decreased (P<0.01),the degree of glomerularsclerosis reduced, the expression of IV collagen and FN in renal tissue was significantly reduced (P<0.01).Conclusion:Curcumin can treatment the DN in db/db mice with type 2 diabetes mellitus, the effection is independent on decreasing glucose.