OBJECTIVETo explore the impact of glycogen synthase kinase-3β (GSK-3β) on Wnt and NF-κB pathways in a rat model of diabetic nephropathy (DN).

METHODSSD rats were randomly divided into normal control group (NC), DN model group (DM) and GSK-3β inhibitor group (DI). Blood glucose and 24-hour urine protein were monitored in three groups. Renal tissue samples were stained by HE. The expression of GSK-3β and NF-κB proteins was studied by immunohistochemistry. GSK-3β and NF-κB mRNAs were detected by RT-qPCR.

RESULTSTen weeks after STZ injection, the level of blood glucose increased significantly in DM group [(23.2±5.4) mmol/L] and DI group [(25.0±4.0) mmol/L], compared with NC group, and the level of 24-hour urinary protein increased significantly in DM group [(185.2±35.6) g/24 h] and DI group [(179.6±44.7) g/24 h], compared with NC group. Two weeks after LiCl injection, the level of blood glucose and 24-hour urinary protein decreased in DI group (17.6±2.1) mmol/L, (106.9±30.0) g/24 h], compared with DM Group. Compared with NC group, pathological changes of the kidney of DM group aggravated along with increased mRNA and protein expression of GSK-3β and NF-κB. But the pathological changes of the kidney in DI group alleviated along with declined mRNA and protein expression of GSK-3β and NF-κB as compared with DM group (all P<0.05).

CONCLUSIONSNF-κB protein expression positively correlates with the GSK3β expression. Wnt and NF-κB signal pathways play an important role in the development of diabetic nephropathy.