糖原合成酶激酶3β和核因子κB在抗体介导的慢性排斥反应移植肾组织中的表达和意义

Expression and significance of GSK-3β and NF-κB in renal tissue with chronic active antibody-mediated rejection

目的:探讨糖原合成酶激酶3β(GSK-3β)、核因子κB(NF-κB)和相关炎症性细胞因子在抗体介导的移植肾慢性排斥反应(cABMR)患者肾组织中的表达情况,并分析其与肾间质纤维化/小管萎缩(IF/TA)的关系。方法:用免疫组织化学技术和计算机真彩色图像分析系统半定量检测116例病理诊断符合ABMR的移植肾组织中GSK-3β、NF-κB p65、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)的表达,并分析其表达与发生ABMR的移植肾组织IF/TA的关系。以10例肾移植术前零点穿刺肾组织作为对照。结果:在抗体介导的慢性排斥反应肾组织中,GSK-3β、NF-κB p65、RANTES和MCP-1表达水平均较对照组明显增高(P均<0.001),且与IF/TA病理分级呈正相关(r分别为0.884、0.914、0.888和0.868,P<0.001),GSK-3β的表达量同NF-κB p65、RANTES和MCP-1表达亦呈正相关(r分别为0.812、0.804和0.788,P<0.001),随着纤维化程度的加重,患者血清肌酐也逐渐升高(r=0.898,P<0.001)。结论:在ABMR患者移植肾组织中,GSK-3β和NF-κB p65的表达异常增高同移植IF/TA、慢性移植肾失功的发生、发展有关。

Objective：To investigate the expression of glycogen synthase kinase-3β （GSK-3β） and NF-κβ in renal allografts with chronic active antibody-mediated rejection （ABMR） and explore its relationship with ABMR induced interstitial fibrosis and tubular atrophy （IF/TA）. Methodology： Immunohistochemical assay and computer-assisted genuine colored image analysis system were used to detect the expressions of GSK-3β and NF-κβ in one hundred and sixteen cases of renal allografts with ABMR. The relationship between expression levels of GSK-3β, NF-κβ, RANTES （regulated on activation, normal T cells expressed and secreted） and MCP-1, interstitial fibrosis and tubular atrophy in renal allografts were analyzed. 10 specimens of healthy renal tissue were used as controls. Results： Compared to the normal tissues,the expressions of GSK-3β, NF-κβ and MCP-1 were significantly higher in the renal tissues with ABMR （P〈0. 001）, and the expressions tended to increase along with the pathological grade of IF/TA, the expression of GSK-3β, NF-κβ, RANTES and MCP-1 were positively correlated with the pathological grades of IF/TA（ r = 0. 884,0. 914, 0. 888 and 0.868 respectively, P 〈 0.001 for all）, the expression of GSK-3β was positively correlated with NF-KB, RANTES and MCP-1 （ r = 0.812,0. 804 and 0. 788 respectively, P 〈 0.001 for all ）, and the serum ereatinine level was also positively correlated with the pathological grades of IF/TA （ r = 0. 898, P 〈0.001）. Conclusion： In renal allograft tissues with ABMR,the up-regulated expressions of GSK-3β and NF-KB may be related to the progressive of the chronic renal allograft dysfunction and allograft fibrosis.