TGF-β1、VEGF在儿童原发性肾病综合征中的表达及其临床意义

Expression of 'TGF-β1 and VEGF and its clinical significance in children with primary nephrotic syndrome

目的研究转化生长因子β1(TGF-β1)和血管内皮生长因子(VEGF)与儿童原发性肾病综合征(PNS) 蛋白尿的关系及其在不同病理类型肾组织中的表达差异,探讨PNS蛋白尿的可能发生机制及导致肾纤维化的影响因素。方法应用ELISA法测定正常对照组与NS组患儿血清TGF-β1、VEGF水平,比较两指标与蛋白尿、肾病不同病理类型间的关系及两者间的相关性;应用免疫组化法检测不同病理类型PNS与正常肾组织中FGF-β1、 VEGF的蛋白表达,并比较其差异。结果①蛋白尿阳性NS组,其血清TGF-β1、VEGF水平均分别较对照组和蛋白尿阴性组显著增高(P<0．05),两指标间呈正相关(r=0.4305)。②在不同病理类型中,局灶节段硬化性肾炎 (FSGS)组粗清TGF-β1水平显著高于微小病变型肾病(MCNS)组、系膜增生型肾小球肾炎(MSPGN)组及对照组 (P<0．01)。③FSGS及MSPGN组血清VEGF水平较MCNS组与对照组显著增高(P<0.05)。④TGF-β1、VEGF 在病变肾组织中阳性表达面积均显著高于对照组(P<0．05)。⑤TGF-β1的蛋白表达强度在MCNS、MSPGN、膜性肾病(MN)、FSGS 4组中呈逐渐增强趋势,其中FSGS组TGF-β1表达较无纤维化组明显增强(P<0．05);而VEGF 蛋白表达强度在不同病理类型之间以及有无间质纤维化之间差异无显著性(P>0．05)。结论①血清TGF-β1、 VEGF水平与PNS蛋白尿的产生有关,且与肾脏病理损害类型有关;②NS患儿肾组织均存在TGF-β1、VEGF蛋白表达增强,尤以TGF-β1表达增强为著,且表达强度可能与小管间质纤维化程度有关。

Objective To explore the relationship ot transtorming growth tactor beta 1 （TGB-β1） and vascular endothelial growth factor（VEGF） with proteinuria in children with primary nephrotic syndrome （PNS） and the discrepancy of TGF-β1 and VEGF expression in renal tissue with varied pathological types confirmed by renal biopsy, and to investigate the mechanism of proteinuria and the risk factors associated with fibrosis in PNS. Methods The levels of serum TGF-β1 and VEGF in peripheral blood by ELISA and the synthesis of TGF-β1 and VEGF in renal tissues with varied pathologic types by immunohistochemistry staining with streptavidin-peroxidase were detected in 28 children with PNS and 10 healthy children, respectively. Results （1） The levels of serum TGF-β1 and VEGF were higher in PNS children with proteinuria than those in either PNS children without proteinuria or normal children （all P〈0.05）, and there was a positive correlation between the levels of TGF-β1 and VEGF（r = 0.4305）. （2） The level of serum TGF-β1 in FSGS group were much higher than those in MCNS group, MSPGN group and control group （all P〈0.01）. （3） The level of serum VEGF were much higher in both of FSGS group and MSPGN group than those in MCNS group and control group （P〈0.01）. （4） The synthetic levels of TGF-β1 and VEGF in renal tissue with varied pathological types were much higher than that in normal renal tissue （P〈0.01）. （5） The synthetic level of TGF-β1 increased gradually in intensity in different nephritic tissues from MCNS group, MSPGN group, MN group to FSGS group, in particular there was a increasing synthetic level of TGF-β1 in FSGS group comparing to those in groups without fibrosis （P〈0.05） . However, there were no significant differences in the synthetic level of VEGF in all groups including varied interstitial fibrosis （P〉0.05）. Conclusions （1） Serum levels of TGF-β1 and VEGF were associated with proteinuria and different pathological types in children with PNS. （2） The synthetic levels of TGF-β1 and VEGF are higher in nephritic tissues with different pathological types, especially there is much higher level of TGF-β1 which can be probably associated with fibroid degree of tubular and interstitialis in children with PNS.