补体旁路途径与经典途径活化在糖尿病肾病进展中的作用  

Alternative and classical complement pathway activation in patients with diabetic kidney

作　　者：杨单植 张颖[1] 权松霞[1] 胡瑞敏[1] 杨杨[1] 杨雨蒙 邢国兰[1] YANG Shan-zhi;ZHANG Ying;QUAN Song-xia;HU Rui-min;YANG Yang;YANG Yu-meng;XING Guo-an(Department of Nephrology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan Province,China)

机构地区：[1]郑州大学第一附属医院肾脏内科,郑州450052

出　　处：《复旦学报（医学版）》2023年第3期370-378,共9页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金面上项目(81870480);国家重点研发计划(2018YFC1314002)。

摘　　要：目的研究补体系统活化成分在糖尿病肾病(diabetic kidney disease,DKD)患者血浆、尿液中的水平,并分析其与DKD临床、病理特征及预后的相关性。方法选取郑州大学第一附属医院经肾穿刺活检证实为DKD患者(DKD组)50例,糖尿病(diabetes mellitus,DM)无肾损害患者(DM组)及健康成年人(健康对照组)各50例,采用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)对血浆及尿液中5种补体成分(H因子、B因子、P因子、C1q、C5a)水平进行了测定。应用COX比例风险回归模型分析影响肾脏预后的独立危险因素,并绘制ROC曲线分析B因子及C5a预测肾脏预后的价值。结果DKD患者血浆中补体B因子、P因子、C1q及C5a均显著高于健康对照组及DM组(P<0.05),H因子低于健康对照组(P=0.03)及DM组(P<0.001)。尿补体B因子、P因子及C5a均显著高于健康对照组及DM组(P<0.05),H因子低于健康对照组(P<0.001)及DM组(P=0.008),3组尿C1q水平无明显差异。旁路途径活化因子H因子、B因子、P因子、C5a水平与蛋白尿程度、肾功能及肾组织病理改变程度有关。多因素Cox风险比例分析显示,尿补体B因子(HR=2.63,95%CI:1.377~5.023,P<0.001)及尿补体C5a(HR=1.33,95%CI:1.06~1.668,P=0.014)是影响肾脏预后的独立危险因素。结论在DKD患者中,补体旁路途径不同程度被激活,且与DKD患者蛋白尿、肾组织病理改变、较差的肾脏预后相关。而补体经典途径起始因子C1q水平与DKD的发生发展及预后无明显相关性。Objective To analyze the levels of components in complement system,in plasma and urine of diabetic kidney disease(DKD)patients,and their correlation with clinical,pathological features and prognosis.Methods The plasma and urine samples of 50 biopsy-diagnosed DKD patients(DKD group)and 50 cases of diabetic patients without no renal injury(DM group)and 50 cases of normal control groups were collected.Five complement components(factor H,factor B,factor P,C1q and C5a)were measured by enzyme-linked immunosorbent assay(ELISA).COX proportional hazard regression model was used to analyze the independent risk factors affecting renal prognosis,and ROC curve was drawn to analyze the value of factor B and C5a in predicting renal prognosis.Results In DKD patients,plasma levels of complement factor B,factor P,C1q and C5a were significantly higher than those in DM group and normal control subjects(P<0.05),factor H was lower than the healthy control group(P=0.03)and the DM group(P<0.001).Urine complement factor B,P factor and C5a were significantly higher than the healthy control group and the DM group(P<0.05),and factor H was lower than the healthy control group(P<0.001)and the DM group(P=0.008).There was no significant difference in the level of urinary C1q among the three groups.The levels of factor H,factor B,factor P and C5a were related to proteinuria,renal function and pathological changes of renal tissue.Multivariate Cox analysis showed that both urinary complement factor B(HR=2.63,95%CI:1.377-5.023,P<0.001)and C5a(HR=1.33,95%CI:1.06-1.668,P=0.014)were independent risk factors for renal prognosis.Conclusion In DKD patients,the alternative complement pathway is activated to varying degrees and is associated with proteinuria,renal histopathological changes,and poor renal prognosis.There was no significant correlation between the levels of classical complement pathway initiation factor C1q and the occurrence,development and prognosis of DKD.

关 键 词：糖尿病肾病(DKD) 补体旁路途径 补体经典途径 肾脏病理 预后 

分 类 号：R587.1[医药卫生—内分泌]