足细胞与Alport综合征蛋白尿的关系

Association between podocytes and proteinuria in Alport syndrome

目的 探讨足细胞与Alport综合征（AS）蛋白尿的关系.方法 AS患者21例,男13例,女8例,根据24 h尿蛋白量将患者分3组,10例＜30 mg/kg为轻度蛋白尿组,4例30～50 mg/kg为中度蛋白尿组,7例＞50 mg/kg为重度蛋白尿组.正常肾组织对照3例.电镜下根据平均足突宽度=л/4×（∑基底膜长度/∑足突个数）,计算每例患者足突宽度.分析足突宽度与蛋白尿关系.用免疫组化方法分析肾组织中裂孔隔膜分子nephrin、podocin和细胞骨架分子synaptopodin的表达.结果 AS患者肾小球足细胞足突宽度（420～2270 nm）与24 h尿蛋白量呈正相关（r=0.765,P＜0.01）.轻度蛋白尿组足突宽度[475（420～900 nm）]显著低于重度蛋白尿组[1520（480～2270）nm]（P＜0.05）.重度蛋白尿组患儿nephrin和podocin表达分布发生改变;表现为弥漫足突融合者synaptopodin表达分布发生改变.2例蛋白尿病程较短（1年）患儿无弥漫足突融合,synaptopodin分布正常,但nephrin和podocin分布异常.结论 肾小球足细胞足突融合、裂孔隔膜及足细胞骨架分子参与AS患儿大量蛋白尿的发生,裂孔隔膜损伤似乎早于足细胞骨架改变.对蛋白尿早期干预可能有助于延缓疾病进展.

Objective To investigate the association between podocytes and proteinuria in children with Alport syndrome. Methods Twenty-one children including 13 boys and 8 girls with Alport syndrome were divided into 3 groups according to 24-hour urinary protein, 〈30 mg/kgas the mild proteinuria group （10 patients）, 30 to 50 mg/kg as the moderate proteinuria group （4 patients） and 〉50 wg/kg as the heavy proteinuria group （7 patients）. The correlation between foot process width and the degree of proteinuria was analyzed. By immunoperoxidase staining on renal tissue, the key slit diaphragm molecules nephrin, podocin and podocyte cytoskeleton-associated molecule synaptopodin were studied. Results The foot process width （420-2270 nm） in patients with Alport syndrome was positively correlated with proteinuria significantly （r=0.765, P〈0.01）.Foot process width was significantly lower in patients with mild proteinuria [475 （420-900） nm）compared with that in patients with heavy proteinuria [1520 （480-2270） nm] （P〈0.05）. In Alport syndrome children with heavy proteinuria, the distribution of nephrin and podocin changed dramatically. In two children with shorter proteinuria period （1 year）, dramatic distribution change of nephrin and podocin occurred, however, the foot process along with synaptopodin preserved.Conclusions Podocyte foot process effacement and injury of slit diaphragm participate in the mechanism of proteinuria in Alport syndrome. The injury of slit diaphragm seems to be an early event in the development of foot process effacement in Alport syndrome, which may guarantee early treatment.