中性粒细胞细胞外网络在ANCA相关性小血管炎患者肾组织中的表达及意义

摘要

Objective: To investigate the expression of Neutrophil Extracellular traps( NETs ) and B lymphocytes in renal tissue of patients with ANCA associated small vasculitis( AASV ) and to investigate its pathogenic mechanism. Methods: Immunohisto-chemistry was used to detect the expression of NETs( citrullinated histone H3 as the marker ) and the infiltration of B lymphocytes ( CD19 as the marker )in renal specimen of the three groups( AASV group, n = 8; minimal change disease ( MCD )group, n = 8; normal control group, n = 3 ). Results:( 1 )The expression of NETs was absent in the renal tissue of the normal control and the MCD group. However, they increased markedly in AASV, especially in areas such as glomeruli with moderate to severe mesangial cells proliferation ( 0.485 ±0.721 ), interstitial areas with inflammatory cell infiltration( 2. 575 ± 2. 99 ), and tubular( 1. 417 ± 2. 888 ). ( 2 ) The expression of B lymphocytes was absent in the renal tissue of the normal control group and the MCD group. However, they increased markedly in AASV, especially in periglomerular areas with glomerulosclerosis ( 4. 024 ±7. 457 ), glomeruli with moderate to severe mesangial cells proliferation( 2. 673 ±2. 948 ), and tubulointerstitial areas with inflammatory cells infiltration( 9. 625 ±8. 961/Hpf ). The expression of B lymphocytes was absent in glomeruli. Conclusion:NETs is widely expressed in the renal tissue of AASV, which may play a role in the damage of renal tissue.%目的:研究中性粒细胞细胞外网络(NETs)在ANCA相关性小血管炎(AASV)患者肾组织中的表达并初步探讨其在AASV中的可能致病机制.方法:采用免疫组织化学技术,分别检测NETs(以瓜氨酸化的组蛋白H3为标志)在8例ANCA相关性小血管炎患者,8例微小病变型肾病综合征患者,3例健康对照的肾小球、肾间质及肾小管的表达,同时检测相应部位B淋巴细胞(CD19做标志)的浸润.结果:(1)AASV患者肾小球中NETs表达较微小病变组患者和健康对照组肾小球中NETs表达明显增多[(0.354±0.347) vs (0±0),P<0.05],在AASV肾脏病理损害严重部位,如中、重度系膜细胞增生的肾小球(0.485±0.721),有炎症细胞浸润的肾间质(2.575±2.99)、肾小管(1.417±2.888)中浸润的NETs明显增多.(2)B淋巴细胞(CD19)的表达:AASV患者肾小球球周B淋巴细胞表达较健康对照组[(3.123±4.411) vs (0±0)]、微小病变组[(3.123±4.411) vs (0±0)]表达明显增多,与微小病变组相比差异有统计学意义(P<0.05).在AASV患者肾组织中主要分布于硬化的肾小球球周(4.024±7.457)、中重度系膜细胞增生的肾小球球周(2.673±2.948),在肾间质炎细胞浸润的区域常成簇聚集(9.625±8.961),而在肾小球内基本无表达.结论:NETs在AASV患者肾组织广泛表达,肾小球中浸润的NETs可能参与了AASV患者的肾损害.