核因子-κB在慢性移植肾失功中作用机制的研究

Expression of NF-κB p65 in Renal Tissue from Patients with Chronic Renal Allograft Dysfunction

目的探讨核因子-κB(NF-κB)及其下游信号分子调节激活正常T细胞表达和分泌的细胞因子(RANTES)和单核细胞趋化蛋白-1(MCP-1)在慢性移植肾失功(CRAD)患者移植肾组织的表达及与肾间质纤维化/小管萎缩(IF/TA)和尿蛋白的关系。方法采用免疫组化技术及计算机真彩色图像分析软件系统半定量检测103例病理诊断符合CRAD的移植肾组织NF-κB p65、RANTES及MCP-1表达量,并分析其表达与CRAD移植肾组织IF/TA、血肌酐及24h尿蛋白的关系。10例移植前零点穿刺正常肾组织作为对照组,入院行血清肌酐及24h尿蛋白定量检测。结果移植肾组织NF-κB p65表达较正常肾组织明显升高[(22.63±6.37)%、(38.59±5.36)%、(53.36±8.77)%比(7.83±0.57)%,P<0.01];其表达水平同炎症细胞趋化因子RANTES、MCP-1及IF/TA病理分级呈正相关(r分别为0.736、0.857和0.904,P均<0.01);NF-κB p65的表达与炎症细胞浸润亦具有正相关性(r=0.851,P<0.01);血肌酐及24h尿蛋白定量的变化随IF/TA病理分级增加而升高(r=0.902和0.870,P均<0.01)。结论在CRAD患者移植肾组织中,NF-κB p65表达明显增强,NF-κB p65及炎症趋化因子的高表达与移植肾间质炎症细胞浸润、肾间质纤维化及慢性移植肾失功等表现密切相关,提示它们可能参与了慢性移植肾功能不全的发生和发展。

Objective To investigate the expression of NF-κB p65 and its downstream signal molecules in renal tissue with chronic renal allograft dysfunction（CRAD）, and explore their relationship with interstitial fibrosis and tubular atrophy（IF/TA） and urine protein. Methods Immunohistochemical assay and computer-assisted genuine colored image analysis system were used to detect the expression of NF-κB p65, regulated on activation normal T cells expressed and secreted（RANTES） and monocyte chemoattractant protein 1（MCP-1） in 103 renal allografts with CRAD. The relationship of NF-κB p65, RANTES, MCP-1 in renal allografts with IF/TA, serum creatinine and24 h urine protein were analyzed. Ten specimens from healthy renal tissue were used as controls. Results Compared to normal tissue, the expressions of NF-κB p65 were significantly higher in renal tissue with CRAD（IF/TAI： 22.63%±6.37%, IF/TA-II： 38.59% ±5.36%, IF/TA-III： 53.36%±8.77% vs control： 7.83% ±0.57%, P 0.001）, and the expressions were positively related to the pathological grade of IF/TA and RANTES and MCP-1（r =0.904,0.736, and 0.857, respectively, all P〈0.001）. The expression of NF-κB p65 was positively related with inflammatory cellular infiltration（r=0.851, P〈0.001）; serum creatinine level and 24 h urine protein were increased with IF/TA grades（r =0.902 and 0.870, all P 0.001）. Conclusion The expression of NF-κB p65 in renal allografts is increased and is closely related to up-regulated RANTES and MCP-1, inflammatory cellular infiltration, IF/TA, and chronic allograft dysfunction. This may indicate the involvement of NF-κB p65 and its downstream signal molecules in progression of chronic renal allograft dysfunction.