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Objective: Diabetic nephropathy (DN) clinical stage occurs hypertension, which is relevant with the enhanced sodium reabsorption in renal tubular.Newly discovered salt-induced kinase 1 (SIK1) not only is involved in glucose and lipid metabolism, and activates Na+-K+-ATPase activity through signaling pathways, leading to high blood pressure.This study investigates the effect of high salt or high fat diet plus streptozotocin (STZ)-induced diabetes leading to diabetic nephropathy ,on the abundance of the renal SIK1 and Na+-K+-ATPase, enzyme activity ofNa+-K+-ATPase and the role of SIK1 in DN with hypertension.Methods: high salt or high fat diet plus STZ induced diatetes(i.v.40mg / kg).only rats with plasma glucose concentrations above 11.1 mmoL / L were considered diabetes.General and laboratory(metabolic and renal) parameters, mean arterial blood pressure and Na+-K+-ATPase activity in rats were measured; pathology of rats kidney was examined with HE and PAS stain under transmission electron microscopy; and the mRNA and protein expression of SIK1 and Na+-K+-ATPase B1 in kidney was detected using RT-PCR and Western blotting.Result: After 4 weeks high salt or high fat diet, 1 week after STZ injection, and 10 weeks after successful model, compared with the normal group, model group rats fasting blood glucose, insulin, cholesterol, triglycerides ester, serum creatinine, urea nitrogen, albumin has increased significantly (P <0.05); insulin sensitivity decreased significantly (P <0.01).The two model groups showed no significant difference.In two models group, blood pressure increased after 8 weeks, 16 weeks of experimental blood pressure of two model groups was significantly higher than normal (P <0.05, P <0.05), no significant difference between the two model groups.Two model groups of renal Na+-K+-ATPasc activity was significantly increased compared with the normal group (P <0.01, P <0.01), no significant difference between the two model groups.Light microscopic examination showed markedly increased glomerular, widened glomerular capsuls and mesangial region, thickened glomerular basement membrane; swelling renal tubular epithelial cells, narrowed lumina, interstitial inflammatory cell infiltration in two model groups.renal SIK1 and Na+-K+-ATPase B1 protein levels were significantly increased (P <0.01, P <0.01), renal SIK1 and Na+-K+-ATPase B1 mRNAlevels were increased (P <0.05), no significant difference between the two model groups.Conclusion: SIK1 mRNAexpression and protein level increased in high salt or high fat diet plus STZ-diabetic rats renal tissue, the model group showed acharacteristic pathological changes of diabetic nephropathy and hypertension, SIK1 itself or may regulate Na+-K+-ATPase activity which involved in the process of diabetic nephropathy with hypertension.