原发性肾病综合征患儿肝细胞生长因子及其受体的表达特征

Expressions of Hepatocyte Growth Factor and Its Receptor in Children with Primary Nephrotic Syndrome

目的观察原发性肾病综合征(PNS)患儿肾组织肝细胞生长因子(HGF)及其受体c-Met的分布及表达,以及血清HGF水平,探讨其在PNS慢性进展中的作用。方法处于PNS活动期的患儿45例。根据肾小管间质损伤程度分为无损伤组7例,轻度损伤组21例,中度损伤组12例,重度损伤组5例。20份正常血清和10例正常肾组织作为对照。应用免疫组织化学及图像分析法观察PNS患儿肾组织HGF、c-Met、转化生长因子-β1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA)表达情况,同时应用双抗体夹心ELISA检测血清HGF水平。组间比较采用单因素方差分析。结果重度损伤组PNS患儿肾组织HGF、c-Met蛋白表达水平明显低于轻度损伤组和中度损伤组(Pa<0.05),与无损伤组比较差异无显著性意义(P>0.05)。PNS患儿肾组织HGF蛋白表达水平与c-Met蛋白表达水平呈显著正相关(r=0.704P<0.01)。HGF蛋白表达水平与TGF-β1、α-SMA蛋白表达水平在重度损伤组中均呈显著负相关(r=-0.945,-0.992Pa<0.01),在轻至中度损伤组中均呈显著正相关(r=0.521,0.603Pa<0.01)。血清HGF水平与肾组织HGF、c-Met蛋白表达水平均呈显著正相关(r=0.721,0.601Pa<0.01)。结论PNS患儿肾组织HGF及其受体c-Met蛋白在损伤肾小管上皮细胞中表达一致增高,提示PNS患儿肾小管上皮细胞是HGF的主要作用部位。PNS患儿肾小管间质病变过程有HGF与TGF-β1的共同参与,二者相关性的变化可能影响肾小管间质病变的结局。

ObjectiveTo observe the expressions of hepatocyte growth factor（HGF） and its receptor c-Met in renal tissues of children with primary nephrotic syndrome（PNS） and the changes of serum HGF,and to explore its role in PNS chronic progress.MethodsForty-five children with PNS in active stage were studied.Among them,5 cases had severe tubulointerstitial lesions,12 cases had moderately tubulointerstitial lesions,21 cases were mild,7 cases without lesions.Serum from 20 normal cases and 10 normal renal tissues were evaluated as well.Inter-group comparison using One-Way ANOVA.Enzyme linked immunosorbent assay（ELISA） was used to examine the serum HGF,and immunohistochemistry staining and image analysis methods were used to study the expressions of HGF,c-Met,transforming growth factor-β,（TGF-β1） and α-smooth muscle actin（α-SMA） in renal tissues.ResultsThe levels of HGF and c-Met protein expressions in renal tissues of children with severe tubulointerstitial lesions were significantly lower than those in the mild group and moderate group（Pa〈0.05）.Compared with those without tubulointerstitial lesions,but the difference had no significance（P〉0.05）.The level of HGF expression had positive correlation with the levels of TGF-β1,α-SMA among children with mild and moderately renal tubulointerstitial lesions（r=0.521,0.603Pa〈0.01）,but negative correlation among the children with severe renal tubulointerstitial lesions（r=-0.945,-0.992Pa〈0.01）.The level of serum HGF had positive correlation with the expressions of HGF protein and c-Met protein in renal tissues（r=0.721,0.601Pa〈0.01）.ConclusionsThe expressions of HGF and c-Met protein in tubular epithelial cell injury in PNS increased consitently,which indicates that HGF playing an important role in tubular epithelial cells in PNS children.HGF and TGF-β1 may be involved in the process of tubulerinterstitial lesions in PNS children,their correlation changes might affect the outcome of renal tubulerinterstitial lesions.