The Expression And Pathological Significance Of Gsk3β In Chronic Allograft Nephropathy Model Of Rats

objective:Set up chronic allograft nephropathy model in rats. To study the expression of GSK3βand NF-κB in chronic allograft nephropathy (CAN) model of rats and to investigate the possible role of GSK3βin CAN.Materials and Methods:Fisher (F344) kidneys were orthotopically transplanted into Lewis rat recipients,to set up chronic allograft nephropathy model in rats. Animals were sacrificed 12 weeks post-transplantation , Renal function and urine protein excretion levels of the rats were analyzed ,and the grafts were harvested for histological study, and expression of GSK3βand NF-κBp65 in renal tissue was analyzed by immunochemistry of SP and Western blot method.Results: 1.In formal test of 40 operations on 80 rats, 34 rats were survived, the operative time of the donor's was 63±17min, and the recipient's was 59±7min, including the warm ischemia time (about 1min), and the cold ischemia time (48±10min). Achievement ratio is about 85%. The abortive cases was anastomosis of both renal veins hemorrhage and thrombosis of renal artery.2. Renal function deteriorated progressively in the CAN group, and there was typical CAN morphology in the kidneys. Biopsies showed mononuclear cell infiltration, thickening of the glomerular basement and tubular basement membrane, associated with interstitial fibrosis and proteinuria.3. GSK3βexpression is substantially increased, mainly located in the cytoplasm of injured tubules. the expression levels of GSK3βand NF-κBp65 in CAN group were significantly higher than isograft group and control group.Conclusions: 1.This method was simple and successfully established rat renal transplantation model of chronic allograft nephropathy and can achieve the requirement of establishing CAN models.2. GSK3βand NF-κB might play an important role in pathogenesis of CAN.3. GSK3βmight regulate NF-κB transcriptional activity on target proinflammatory gene expression.