激素耐药性肾病综合征肾小管上皮细胞-间充质转化临床意义研究

探讨肾小管上皮细胞-间充质转化（EMT）与肾脏病理进展及原发性肾病综合征（INS）糖皮质激素（GC）耐药的关系。方法　2005年9月至2007年12月在中南大学湘雅二医院儿科住院行肾穿刺活检的INS患儿40例，分为激素耐药性肾病综合征（SRNS）组（20例）和激素敏感性肾病综合征（SSNS）组（20例）。免疫组化双染法检测INS患儿和5例正常对照组儿童肾组织中细胞角蛋白（CK）和波形蛋白（vimentin）的表达，肾脏病理评分半定量评价肾组织病理损害程度。结果　SRNS组肾小管-间质病理评分显著高于SSNS组（P < 0.05）；正常对照组肾小管上皮细胞内只表达CK，不表达vimentin；INS肾小管上皮细胞均不同程度表达vimentin；SRNS组肾组织CK表达较SSNS组显著降低[分别为（66.25±12.13）%和（76.64±7.64）%，P < 0.05]，vimentin表达较SSNS组显著增高[分别为（11.51±7.48）%和（4.98±2.27）%，P < 0.05]；不同肾小管-间质病变（轻、中、重度）组肾小管上皮细胞内CK和vimentin表达量的差异均有统计学意义[CK表达量分别为（79.97±3.70）%、（65.47±7.93）%和（48.47±5.98）%，P < 0.05]；vimentin表达量分别为（4.74±1.84）%、（9.65±5.10）%、（23.60±7.72）%，P < 0.05]；肾小管-间质病理评分与肾小管上皮细胞CK表达呈负相关（r = -0.887，P < 0.01），与vimentin的表达呈正相关（r = 0.868，P < 0.01）。结论 　肾病综合征肾组织的肾小管上皮细胞存在不同程度的肾小管上皮细胞-间充质细胞转化（EMT）现象，尤以SRNS为甚；检测肾组织EMT水平可能有助于判断INS的预后。

Significance of epithelial to mesenchymal transition in children with steroid-resistant nephrotic syndrome.

Objective　To study the relationship of epithelial to mesenchymal transition with renal pathological progression and slucocorticoidresistance in idiopathic nephrotic syndrome. Methods　The different expressions of CK and vimentin were detected with theimmunohistochemistry double staining technique in renal biopsy tissues obtained from 20 SRNS children，20 SSNS children and 5 nephrectomizedhealthy children， respectively. Renal histopathological lesion was evaluated by the semi-quantitative counting scores. Results　Thetubulointerstitial pahological counting scores in SRNS group was higher than that in SSNS group （P < 0.05）. There was no vimentin but CKexpression on the tubular epithelium in the control group and different levels of expression of vimentin were found in INS group. In SRNSgroup，the expression of CK was lower than SSNS group [（66.25±12.13）% ，（76.64±7.64），P < 0.05] and the expression of vimentin washigher than SSNS group [（11.51±7.48）%， （4.98±2.27）％， P < 0.05]. With the raising grade of tubulointerstitial lesions （graded asmild， moderate and severe lesions），the expression of vimentin was increased wheres expression of CK was decreased [vimentin， （4.74±1.84）％，（9.65±5.10）％，（23.60±7.72）％， P < 0.05]； CK，（79.97±3.70）％，（65.47±7.93）％，（48.47±5.98）％，P < 0.05]. The countingscores of the tubulointerstitial lesions were positively correlated with the level of vimentin expression（r = 0.868，P < 0.01）， butnegatively correlated with CK expression level in renal tissues （r = -0.887，P < 0.01）. Conclusion　The phenomenon of EMT existsdifferently in renal tissues of INS cases and the degree of those is higher in SRNS group. The detection of EMT in renal tissues can beadopted to tell the different prognoses in INS.