Expressions And Significance Of Nuclear Transcription Factor-kappaBp65,Nitric Oxide Synthase And Vascular Endothelial Growthfactor In Glomeruli Of Patients With Idiopathic Membranous Nephropathy

Objective : To explore the expression of nuclear transcription factor-kappaB p65(NF-κB p65),nitric oxide synthase(iNOS,eNOS,nNOS) and vascular endothelial growthfactor(VEGF) in the glomerulus of patients with idiopathic membranous nephropathy(IMN), and its relationship with albuminuria and serum creatinine. Moreover to detect the contents of NOS and NO in the urinary. To deeply understand the contributions of NF-κB p65,NOS,NO and VEGF to the IMN. Quibus to explore the target of IMN therapic.Methods:Immunohistochemistry was applied to detect the expression of NF-κB p65,NOS,NO and VEGF in renal glomerulus of patients with the IMN(Ⅰ,ⅡandⅢstage) (IMN groups) and the normal renal glomerulus of patients with benign oncokidney (control group). To detect the changes of urinary NOS and urinary NO of patients with IMN groups and control group.Results:1 NF-κB p65 was expressed, at a low level, in tubular epithelial cells and podocytes of control group. NF-κB p65 was expressed in tubular epithelial cells and podocytes of every IMN groups. The expression of NF-κB p65 in glomerulus ofⅠstage IMN group significantly increased as compared to the control group (P<0.001); The expression of NF-κB p65 in glomerulus ofⅡstage IMN group significantly increased as compared to the control group (P<0.001). In comparison withⅠstage IMN group, the expression of NF-κB p65 ofⅡstage MN group was increased (P<0.05).2 iNOS was expressed, at a low level, in tubular epithelial cells and podocytes of control group. iNOS was expressed in endothelial cells,podocytes,mesangial cells,proximal and distal convoluted tubular epithelial cells of every IMN groups. eNOS was expressed in endothelial cells and tubular epithelial cells of control group and every IMN groups. nNOS was expressed in tubular epithelial cells and podocytes of control group and every IMN groups. The expression of iNOS,eNOS and nNOS in glomerulus ofⅠandⅡstage IMN groups increased as compared to the control group (P<0.001;P<0.05;P<0.01). In comparison withⅠstage IMN group, the expression of iNOS ofⅡstage MN group was significantly increased (P<0.001).3 VEGF was expressed, at a low level, in podocytes and tubular epithelial cells of control group. VEGF was expressed in podocytes,endothelial cells,mesangial cells and tubular epithelial cells of every IMN groups. The expression of VEGF in glomerulus ofⅠstage IMN group increased as compared to the control group (P<0.001); The expression of VEGF in glomerulus ofⅡstage IMN group increased as compared to the control group (P<0.05). In comparison withⅠstage IMN group, the expression of VEGF ofⅡstage MN group was significantly decreased (P<0.01).4 In IMN group the expression of NF-κB p65 positively correlated with the expression of iNOS (r=0.61,P<0.01), and no correlated with eNOS and nNOS; InⅠstage IMN group the expression of NF-κB p65 positively correlated with the expression of iNOS (r=0.48,P<0.01), and no correlated with eNOS and nNOS; InⅡstage IMN group the expression of NF-κB p65 positively correlated with the expression of iNOS (r=0.86,P<0.05), and no correlated with eNOS and nNOS. In IMN group the expression of VEGF positively correlated with the expression of iNOS (r=0.32,P<0.01), and no correlated with eNOS and nNOS; InⅠstage IMN group the expression of VEGF positively correlated with the expression of iNOS (r=0.92,P<0.01), and no correlated with eNOS and nNOS; InⅡstage IMN group the expression of VEGF no correlated with the expression of iNOS,eNOS and nNOS. In IMN groups the expression of NF-κB p65 no correlated with the expression of VEGF; InⅠstage IMN group the expression of NF-κB p65 positively correlated with the expression of VEGF (r=0.49,P<0.01); InⅡstage IMN group the expression of NF-κB p65 no correlated with the expression of VEGF.5 The urinary NO of patients with IMN groups increased as compared to the control group (P<0.05), and positively correlated with the Urine protein quantitation in 24 hours (r=0.50,P<0.01); the urinary NO ofⅠstage IMN group positively correlated with the Urine protein quantitation in 24 hours (r=0.38,P<0.05); the urinary NO ofⅡstage IMN group positively correlated with the Urine protein quantitation in 24 hours (r=0.87,P<0.05). The urinary total NOS of patients with IMN groups increased as compared to the control group (P<0.01), and positively correlated with the Urine protein quantitation in 24 hours (r=0.38,P<0.05); the urinary total NOS ofⅠstage IMN group positively correlated with the Urine protein quantitation in 24 hours (r=0.40,P<0.05); the urinary total NOS ofⅡstage IMN group no correlated with the Urine protein quantitation in 24 hours. The urinary iNOS of patients with IMN groups increased as compared to the control group (P<0.05), and positively correlated with the Urine protein quantitation in 24 hours (r=0.52,P<0.01); the urinary iNOS ofⅠstage IMN group positively correlated with the Urine protein quantitation in 24 hours (r=0.42,P<0.05); the urinary iNOS ofⅡstage IMN group positively correlated with the Urine protein quantitation in 24 hours (r=0.85,P<0.05).6 In IMN groups the expression of iNOS positively correlated with the Urine protein quantitation in 24 hours (r=0.50,P<0.01;Ⅰstage IMN group the expression of iNOS positively correlated with the Urine protein quantitation in 24 hours r=0.49,P<0.01;Ⅱstage IMN group the expression of iNOS positively correlated with the Urine protein quantitation in 24 hours r=0.82,P<0.05), and negatively correlated with the level of serum creatinine (r=-0.04,P<0.05),serum creatinine(r=-0.39,P<0.05) and blood uric acid(r=-0.60,P<0.01). In IMN groups the expression of eNOS positively correlated with the Urine protein quantitation in 24 hours (r=0.44,P<0.01;Ⅰstage IMN group the expression of eNOS positively correlated with the Urine protein quantitation in 24 hours r=0.50,P<0.01;Ⅱstage IMN group the expression of eNOS no correlated with the Urine protein quantitation in 24 hours). In IMN groups the expression of NF-κB p65 positively correlated with the Urine protein quantitation in 24 hours (r=0.63,P<0.01;Ⅰstage IMN group the expression of NF-κB p65 positively correlated with the Urine protein quantitation in 24 hours r=0.54,P<0.01;Ⅱstage IMN group the expression of NF-κB p65 positively correlated with the Urine protein quantitation in 24 hours r=0.89,P<0.05) and the level of Blood urea nitrogen (r=0.35,P<0.05), and negatively correlated with the level of serum creatinine (r=-0.52,P<0.01) and blood uric acid(r=-0.34,P<0.05). In IMN groups the expression of VEGF no correlated with the Urine protein quantitation in 24 hours; inⅠstage IMN group the expression of VEGF correlated with the Urine protein quantitation in 24 hours(r=0.38,P<0.05); inⅡstage IMN group the expression of VEGF no correlated with the Urine protein quantitation in 24 hours.7 Urine protein quantitation in 24 hours of IMN groups were obviously increased as compared to the control group (P<0.01).Conclusions:The high expression of NF-κB p65 in glomerulus of patients with IMN up-regulated the expressions of iNOS and NO, positively correlated with the Urine protein quantitation in 24 hours. Moreover the expression of iNOS and NO up-regulated the expression of VEGF, no correlated with the Urine protein quantitation in 24 hours.