紧密连接蛋白claudin-2在急性肾损伤患儿肾组织中的表达及意义

Expression of tight junction protein claudin-2 in renal tissues and its significance in children with acute kidney injury

摘要:

目的 研究紧密连接蛋白claudin-2在急性肾损伤（AKI）患儿肾组织中的表达变化，探讨claudin-2与肾脏病理损害及肾功能损害程度的关系。方法 2009年12月至2011年12月确诊为AKI并完善肾活检的24例患儿，依据病情严重程度分为轻症组（n=7）及重症组（n=17）。对照组为12例肾小球轻微病变的孤立性血尿患儿。采用全自动生化分析仪比色法检测血清肌酐水平；采用肾脏病理计量评分法对肾小管间质损害程度进行分析；免疫组织化学方法 检测肾组织claudin-2的表达；Pearson相关分析评估claudin-2与患儿肾脏病理评分及血肌酐水平间的关系。结果 AKI轻症组（190±68 μmol/L）与AKI重症组（477±128 μmol/L）血清肌酐水平均高于对照组（29±7 μmol/L）（均P<0.01），且AKI重症组血清肌酐水平高于AKI轻症组（P<0.01）。AKI轻症组患儿肾小管间质损害计分（10.4±1.7分）低于重症组（14.0±1.5分）（P<0.05）。AKI轻症组（5.0%±0.5%）与AKI重症组（3.7%±0.7%）claudin-2阳性表达面积均低于对照组（8.0%±0.7%）（均P<0.01），且AKI重症组claudin-2阳性表达面积低于AKI轻症组（P<0.01）。claudin-2阳性表达面积与血肌酐水平及肾小管间质的病理损害评分均呈负相关（分别r=-0.809、-0.903，均P<0.01）。结论 AKI患儿肾组织claudin-2的表达水平发生变化，且claudin-2的表达水平与肾脏病理损害程度及肾功能损害程度密切相关。

Abstract:

Objective To examine changes in expression of tight junction protein claudin-2 in the renal tissues of children with acute kidney injury (AKI), and to investigate the relationship of claudin-2 expression with renal pathological lesion and renal functional lesion. Methods Twenty-four children who were diagnosed with AKI and had renal biopsies between December 2009 and December 2011 were included in the study. These patients were divided into mild AKI (n=7) and severe AKI groups (n=17). Children with isolated hematuria whose renal biopsy showed minor glomerular lesion were selected as the control group. Serum creatinine levels were measured by automatic biochemical analyzer. Tubulointerstitial damage was evaluated by renal pathological scores and expression of claudin-2 was examined by immunohistochemistry. The correlations of claudin-2 expression with renal pathological score and serum creatinine level were assessed by Pearson correlation analysis. Results The mild and severe AKI groups had significantly higher serum creatinine levels than the control group (190±68 μmol/L and 477±128 μmol/L vs 29±7 μmol/L, P<0.01), and the severe AKI group had a significantly higher serum creatinine level than the mild AKI group (P<0.01). The tubulointerstitial damage score was significantly lower in the mild AKI group than in the severe AKI group (10.4±1.7 vs 14.0±1.5; P<0.05). The mild and severe AKI groups had significantly smaller areas of claudin-2 expression than the control group (5.0±0.5% and 3.7±0.7% vs 8.0±0.7%; P<0.01), and the severe AKI group had a significantly smaller area of claudin-2 expression than the mild AKI group (P<0.01). The area of claudin-2 expression was negatively correlated with serum creatinine level and tubulointerstitial damage score (r=-0.809 and -0.903; P<0.01). Conclusions There are changes in the distribution and expression of claudin-2 in proximal tubular epithelial cells among children with AKI, and claudin-2 expression is closely related to renal pathological lesion and renal functional lesion.