P因子介导的C5a/C5aR轴活化在IgA肾病肾脏足细胞损伤中的作用

Role of C5a/C5aR axis activation mediated by factor P in podocyte injury of IgA nephropathy

目的:研究P因子介导的C5a/C5aR轴活化在IgA肾病肾脏足细胞损伤中的作用。方法:选取在郑州大学第一附属医院肾内科住院的少量、中量、大量蛋白尿IgA肾病患者各20例,收集其血液、尿液和肾组织标本;肾脏肿瘤切除术患者(20例)的远离肿瘤组织5 cm以上、病理诊断为正常的肾组织为对照1组,20例体检健康的成人血液、尿液标本为对照2组。电镜观察肾脏足细胞损伤程度,行Tunel和Nephrin共染色观察足细胞凋亡情况;免疫荧光法观察肾组织中足细胞P因子或C5aR、C5b-9与Nephrin共表达的情况;采用ELISA法检测IgA肾病组和对照2组血清及尿液中的P因子水平。结果:(1)大量蛋白尿IgA肾病患者肾组织足细胞足突弥漫融合、足细胞凋亡明显增加,Nephrin表达降低。(2)大量蛋白尿IgA肾病组患者足细胞上的P因子、C5aR和C5b-9表达明显增强、Nephrin表达减弱。(3)大量蛋白尿IgA肾病组患者较对照2组血清、尿液P因子水平升高。结论:P因子介导的C5a/C5aR轴过度活化可能参与了IgA肾病肾脏足细胞损伤的发生。

Aim:To explore the role of C5a/C5aR axis activation mediated by factor P in podocyte injury of IgA nephropathy.Methods:The blood, urine and renal tissue samples of each 20 IgA nephropathy patients with mild, moderate and massive proteinuria in the Department of Nephrology, the First Affiliated Hospital of Zhengzhou University were collected.The normal renal tissues(more than 5 cm away from the tumor tissue and confirmed by pathology) of 20 patients with renal tumor was control group 1,while the blood and urine samples of 20 healthy adults were control group 2.Electron microscope was used to observe the degree of podocyte injury.Tunel and Nephrin co-staining was used to count podocyte apoptosis.Immunofluorescence was used to detect the co-expression of factor P or C5aR,C5b-9 and Nephrin in nephrotic podocytes.ELISA was used to detect the factor P level in serum and urine of case group and control group 2.Results:In IgA nephropathy patients with massive proteinuria, the podocytes were diffusely fused, the apoptosis of podocytes was significantly increased, and the expression level of Nephrin was decreased.The expressions of factor P,C5aR and C5b-9 on the podocytes of IgA nephropathy patients with massive proteinuria were significantly increased, while the expression of Nephrin was weakened.Compared with the control group 2,the serum and urine factor P levels of IgA nephropathy patients with massive proteinuria were significantly higher.Conclusion:The excessive activation of C5a/C5aR axis mediated by factor P may be involved in the occurrence of podocyte injury in IgA nephropathy.