Expression Of DKK1、β-catenin In Kidney Of Diabetic Rats And Effect Of Cordyceps Sinensis

ObjectiveTo observe the expressions of Dickkopf-1(DKK1), β-catenin and fibronectin(FN) in diabetic rats and to study the changes of DKK1, β-catenin and FN after treated by Cordyceps sinensis, and to investigate the most possible protective mechanisms of Cordyceps sinensis on Diabetic Nephropathy (DN).MethodsTwelve rats were randomly elected from forty male Wistar rats as normal group. The others were treated with intraperitoneal injection of60mg/kg streptozotocin to induce diabetes. Blood glucose level in tail venous blood samples was measured in each rat after72hours. Twenty six rats with high postfasting blood glucose (>16.7mmol/L) were randomly divided into two groups for subsequent experiments: model group (n=13) and Cordyceps sinensis treatment group (n=13). Rats in treatment group were given a daily Cordyceps suspension(5mg/kg/d) fed. The normal group and model group were given an equal dose of double-distilled water gavage. In the end of12weeks, twelve rats of each group were sacrificed. The levels of blood glucose, urinary albumin to creatinine ratio (UACR) and creatinine clearance rate (Ccr) were determined. Expressions of DKK1, P-catenin and FN in renal tissue were measured by immunohistochemistry and real-time quantitative PCR. DKK1protein expression was further examined by Western blot.ResultsCompared with normal group, model group had decreased body weight, but significantly increased kidney index, concentrations of blood glucose, UACR and Ccr (p<0.05). The mRNA and protein levels of DKK1and FN were also elevated. Immunohistochemistry showed that β-catenin staining was significantly impaired in model group (p<0.05). HE staining showed that there were hypertrophy of glomerular, expansion of the mesangium and thickening of glomerular basement membrane.Cordyceps sinensis treatment decreased the levels of kidney index, Ccr and UACR (p<0.05), but did not significantly altered blood glucose concentrations (p>0.05). After treatment with Cordyceps, the expressions of DKK1and FN were decreased (p<0.05), the protein level of β-catenin was increased significantly (p<0.05).ConclusionsIn the early stage of DN, the levels of Ccr and UACR are obviously increased. Glomerulus is large. Glomerular mesangium are expansive and basement membrane are thickened slightly. Increased expressions of DKK1and reduced β-catenin protein are involved in diabetic nephropathy.After treatment with Cordyceps sinensis, the levels of Ccr and UACR were decreased. Cordyceps sinensis treatment can decrease the expression of DKK1and increase the level of β-catenin protein. Cordyceps sinensis may prevents the FN accumulation in diabetic rats through downregulation of DKK1expression and stabilization of β-catenin protein.