基于尿蛋白质组学探究凉血解毒活血法联合西医治疗IgA血管炎肾炎Ⅲ级病变的疗效特点  

Study on therapeutic effect characteristics of Liangxue Jiedu Huoxue method combined with western medicine on IgAV nephritis gradeⅢbased on urinary proteomics

作　　者：张冰[1,2] 黄岩杰[1,3] 张秋爽 侯改灵 宋兰 ZHANG Bing;HUANG Yanjie;ZHANG Qiushuang;HOU Gailing;SONG Lan(Department of Pediatrics,the First Affiliated Hospital of Henan University of CM,Zhengzhou 450000,China;College of Pediatrics,Henan University of Chinese Medicine,Zhengzhou 450046,China;Shanghai Children's Hospital/Children's Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200062,China;Beijing Proteome Research Center,Beijing 102206,China)

机构地区：[1]河南中医药大学第一附属医院儿科医院,郑州450000 [2]河南中医药大学儿科医学院,郑州450046 [3]上海市儿童医院/上海交通大学医学院附属儿童医院,上海200062 [4]北京蛋白质组研究中心,北京102206

出　　处：《中华中医药杂志》2024年第8期4469-4473,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.82174187);河南省中医药学科领军人才(No.豫卫中医函[2021]8号);2022年中原科技创新领军人才(No.234200510028)。

摘　　要：目的:利用尿蛋白质组学探究凉血解毒活血法联合西医治疗对IgA血管炎肾炎(IgAVN)Ⅲ级病变的疗效特点。方法:发现队列收集20例IgAVNⅢ级患儿治疗前及治疗后1个月的尿液,利用液相色谱-串联质谱的方法进行尿蛋白质谱检测,筛选差异蛋白并进行生物信息学分析。在验证队列,检测30例IgAVNⅢ级患儿治疗前后尿液中24 h尿蛋白定量(24h-UPRO)、尿红细胞计数(URBC)的水平及差异蛋白α2巨球蛋白(A2M)的浓度。结果:以蛋白变化倍数>2或<0.5,且P<0.05为差异蛋白筛选标准,共获取93个显著上调蛋白和27个显著下调蛋白。富集分析结果表明,下调差异蛋白在补体激活-经典途径、凋亡细胞清除的正调控、先天免疫反应、补体和凝血级联、产生IgA的肠道免疫网络等生物学过程和通路显著富集。治疗1个月后,IgAVNⅢ级患儿24h-UPRO、URBC水平较治疗前显著降低(P<0.01,P<0.05)。验证结果显示,与治疗前比较,中西医治疗后的尿A2M/Cr水平显著降低(P<0.01)。结论:凉血解毒活血法联合西医治疗能够抑制免疫及凝血相关通路,药理机制可能是通过抑制A2M,降低IgAVNⅢ级病变的免疫炎症,改善高凝状态,进而减少尿蛋白和尿红细胞,减轻肾脏损伤。Objective: To explore the therapeutic effect of Liangxue Jiedu Huoxue method combined with western medicine on immunoglobulin A vasculitis nephritis(IgAVN) grade Ⅲ. Methods: Urine samples were collected from 20 children with IgAVN grade Ⅲ before and 1 month after treatment in the discovery cohort. The urine protein was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS), and the differential proteins were screened and bioinformatics analyzed. In the validation cohort, the 24 h urinary protein(24h-UPRO), urine red blood cell(URBC) and the concentration of α2-macroglobulin(A2M) in urine of 30 children with IgAVN grade Ⅲ was determined before and after treatment. Results:Fold change>2 or <0.5 and P<0.05 were used as screening criteria for differential proteins. A total of 93 significantly upregulated proteins and 72 significantly down-regulated proteins were obtained. Analysis showed that the differential proteins were significantly enriched in complement activation, classical pathway, positive regulation of apoptotic cell clearance, innate immune response, complement and coagulation cascades and intestinal immune network for IgA production pathways. After 1 month of treatment, the levels of 24h-UPRO, URBC were significantly lower than those before treatment(P<0.01, P<0.05). After treatment,the urinary A2M/Cr level significantly decreased(P<0.01). Conclusion: Liangxue Jiedu Huoxue method combined with western medicine can inhibit immune and coagulation-related pathways. The pharmacological mechanism may be through inhibiting A2M,reducing the immune inflammation of IgAVN grade Ⅲ lesions and improving the hypercoagulability, and then reducing the urine protein and urine red blood cells, alleviating the renal injury.

关 键 词：IgA血管炎肾炎 蛋白质组学 凉血解毒活血法 免疫反应 凝血 

分 类 号：R692.31[医药卫生—泌尿科学]