Sulodexide prevents diabetic nephropathy through inhibiting renal NF-κB activation and MCP-1 expression / 中华肾脏病杂志

ABSTRACT

Objective To study the effects of sulodexide on renal NF-κB activation and monocyte chemotactic protein 1 (MCP-1) expression in diabetic rats and elucidate the possible mechanism of sulodexide in preventing diabetic nephropathy (DN). Methods Wistar rats were fed with high-sucrose-high-fat diet and injected with a low dose of STZ (streptozotocin,35 mg/kg) into abdominal cavity to induce diabetes.DM rats were randomly divided into non-treated group of treatment,blood glucose (BG),triglyceride (TG),cholesterol,serum creatinine (Scr),urea nitrogen (BUN),24 h urinary albumin excretion (UAE) were measured.HE staining was performed in renal tissues for light microscopy examination of mean glomerular volume (MGV).MCP-1 expression was detected by immunohistochemical method.NF-κB activation was determined by Western blot. Results Compared with NC group,DM group and DMS group had significant elevated BG,TG and TC levels (all P＜0.01).There were no significant differences of BG,TG or TC levels between DM group and DMS group.Compared with NC group,DM group and DMS group had significant increased Scr,BUN,UAE levels (all P＜0.01).Scr,BUN,UAE levels were significantly lower in DMS group than those in DM group [(39.1±0.88) μmol/L vs (41.0±2.16) μmol/L,(9.12±1.06) mmol/L vs (9.87±0.19) mmol/L； (19.92±0.96) mg/24 h vs (25.99±0.52)mg/24 h,all P＜0.05].Compared with NC group,the MGV of DM group was significantly increased [(7.47±1.11)×105 μm3 vs (4.22±1.09)×105 μm3,P＜0.01].Compared with DM group,the MGA of DMS group was significantly reduced [(6.64±0.71)×105 μm3 vs (7.47±1.11)×105 μm3,P＜0.05],but was still increased compared with that of NC group (P＜0.01).Compared with NC group,the MCP-1 expression of DM group was significantly higher [(12.17±1.94)/HPF vs (1.19±0.70)/HPF,P＜0.01].MCP-1 expression in DSM group was significantly lower than that of DM group [(9.22± 1.61)/HPF vs (12.17±1.94)/HPF,P＜0.01],but still higher than that of control group (P＜0.01).Compared with NC group,the NF-κB activity was significantly higher in DM group [(0.89±0.07) vs (0.24±0.03),P＜0.01].Compared with DM group,NF-κB activity of DMS group was significantly lower [(0.27±0.01) vs (0.89±0.07),P＜0.01].There was no significant difference of NF-κB activity between DMS group and NC group. Conclusion Sulodexide has protective effects on diabetic nephropathy,and one of the mechanisms may involve the inhibition of NF-κB activation as well as the suppression of MCP-I expression.