The Role Of NF-κB In The Progression Of Aldosterone-induced Renal Injury And Its Involved Mechanisms

PARTⅠThe role of NF-κB in the Progression of Aldosterone-induced Renal InjuryObjective:Aldosterone has been suggested to be involved in the progression of fibrosis of multiple organs. So aldosterone induced renal injury and the mechanism of aldosterone in the progression of CKD has been a research focus. NF-κB constitutively expressed in almost all nucleated cells. Activated NF-κB translocate into nucleus, then combine with corresponding target genes, regulate its transcription and expression. Activation of NF-κB has been observed in association with many renal disease models, and inhibition of the NF-κB could significantly attenuate renal injury. Hence, in this part we investigated the role of NF-κB in the progression of aldosterone-induced renal injury.Methods:32 male SD rats were uninephrectomized. One week later, rats were equally devided into four groups randomly:control group, high-salt group (1%Nacl in chow), aldosterone group (1%Nacl in chow,0.75ug/h aldosterone delayed relase by osmotic mini-pump, subcutaneous), PDTC group (1%Nacl in chow,0.75ug/h aldosterone, 100mk/kg PDTC, by gavage). All rats were treated for 4 weeks. SBP, urinary protein volume, renal function and renal morphology were all observed. The activity of NF-κB in renal cortex were detected by electrophoretic mobility shift assay (EMSA). Moreover, the location of NF-κB was measured by Immunohistochemisty.Results:Rats of aldosterone group exhibited higher blood pressure and more serious renal injury characterized by proteinuria, glomerular sclerosis compared with rats of the high-salt group. Moreover, all these changes were accompanied with an increase in NF-κB activity. Treatment with PDTC which is a specific inhibitor of NF-κB notably alleviated SBP, proteinuria and glomerular sclerosis in aldosterone-infused rats.Conclusion:The activation of NF-κB was involved in aldosterone/salt induced renal injury. PARTⅡInvolved Mechanisms of NF-κB in the Progression of Aldosterone-induced Renal InjuryObjective:In the partⅠwe have found that the NF-κB was activated in aldosterone/salt induced renal injury. Inhibition of NF-κB by PDTC was accompanied with attenuation of renal injury. But the mechanisms involved in aldosterone/salt induced renal injury was unclear. So, this part is to investigate the possible mechanisms.Methods:The expression of CTGF and ICAM-1 were measured by westernblot and real-time PCR, and TGF-β、collagenⅣwere aslo measured by real-time PCR. Moreover, the expression of CTGF and collagenⅣwere measured by Immunohistochemisty.Results:ICAM-1 and CTGF, protein and mRNA levels, were significantly increased in aldosterone group rats than in the high-salt group rats. In addition, TGF-βand collagenⅣmRNA levels were also increased, the expression of CTGF and TGF-βin cortex were elevated. Furthermore, PDTC markedly decreased the expression of CTGF, ICAM-1, TGF-β, collagenⅣ.Conclusion:CTGF, ICAM-1, TGF-β, collagenⅣwere substantially involved in aldosterone/salt induced renal injury via activation of NF-κB-dependent pathway.