整合素连接激酶在抗体介导的慢性排斥反应患者肾组织中的表达及意义

Expression and significance of integrin-linked kinase in renal tissues of patients with chronic active antibody-mediated rejection

目的研究移植肾组织中整合素连接激酶(ILK)及Ⅳ型胶原、转化生长因子β1(TGF-β1)表达和抗体介导的慢性排斥反应的关系。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46例抗体介导的慢性排斥反应(Chronic active antibody-mediated rejection,ABMR)患者移植肾组织中ILK、Ⅳ型胶原和TGF-β1的表达情况,分析3者间及与ABMR的间质纤维化与肾小管萎缩(IF/TA)的病理分级之间的关系。15例正常肾组织作为对照。结果 ABMR移植肾组织中ILK、Ⅳ型胶原、TGF-β1的表达比正常肾组织明显增加(P<0.001),并随ABMR中IF/TA病理分级呈逐渐递增的趋势。移植肾组织中ILK的表达与TGF-β1、Ⅳ型胶原呈正相关(r分别为0.830、0.707,P<0.001)。结论 ILK可能是介导TGF-β1促进移植肾间质纤维化细胞外基质(extracellular matrix,ECM)异常沉积的发病机制,Ⅳ型胶原的异常沉积是ABMR中IF/TA患者移植肾纤维化的重要表现。转化生长因子β1已经证明了与移植肾纤维化显著的相关性,ILK在抗体介导的排斥反应的移植肾纤维化进程中起重要作用。

Objective To investigate the expression of integrinlinked kinase（ILK） and collagen Ⅳ in the renal allografts of patients with chronic active antibody-mediated rejection（ABMR） of interstitial fibrosis and tubular atrophy（IF/TA）, and explore its relationship with transforming growth factor-β1 （TGF-β1） expression and the pathogenesis in ABMR of IF/TA. Methods Immunohistochemical assay and computer-assisted genuine colored image analysis system were used to detect the expression of ILK, TGF-β1 and collagen Ⅳ in the renal allografts of patients with IF/TA of ABMR. The association between TGF-β1,collagen Ⅳ and ILK, and the relationship between their expressions and IF/TA,pathological class of ABMR, were analyzed. 15 specimens of healthy renal tissue which come from pretransplant were used as controls. Results Compared to normal renal tissues, the expressions levels of ILK, TGF-β1 and collagen Ⅳ were significantly higher in the renal tissues of the patients （P0.001）,and the expressions tended to increase with the pathological grades of IF/TA. In IF/TA group,the expression of ILK was positively correlated with that of TGF-β1 and collagen Ⅳ（r=0.830 and r=0.707,respectively;P0.001 for both）. Conclusion By the data it is indicated that ILK might mediate the mechanism through which TGF-β1 promote the abnormal deposition of ECM in renal allograft with IF/TA and the abnormal deposition of collagen Ⅳ in renal allograft might be important manifestation of fibrosis in IF/TA. It is suggested that ILK might play an important role in the progression of renal fibrosis in IF/TA of chronic active antibody-mediacted rejection and the chronic renal allograft dysfunction.