中性粒细胞胞外诱捕网浸润促进尿道创伤后尿道成纤维细胞活化和增生性瘢痕形成  

Infiltration of neutrophil extracellular traps promotes activation of urethral fibroblasts and scar formation after urethral trauma

作　　者：陈烨辉 许以城 阮中天 林婷婷[1] 薛学义[1] 许宁[1] CHEN Yehui;XU Yicheng;RUAN Zhongtian;LIN Tingting;XUE Xueyi;XU Ning(Departments of Urology,The First Affiliated Hospital of Fujian Medical University,Fuzhou 350005,China)

机构地区：[1]福建医科大学附属第一医院泌尿外科,福建福州350005

出　　处：《中国病理生理杂志》2024年第1期103-109,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81970589);福建省财政专项(No.2019B030)。

摘　　要：目的:探讨中性粒细胞胞外诱捕网(NETs)对创伤后尿道瘢痕形成的影响。方法:(1)2021年6月至2022年12月,收集福建医科大学附属第一医院泌尿外科患者的临床样本,比较尿道创伤患者(n=20)与健康志愿者(n=20)血液和尿液NETs水平的差异,并分析其与尿道瘢痕形成的关系。(2)从尿道瘢痕组织中提取原代尿道成纤维细胞,体外诱导中性粒细胞以获得NETs,分别以生理盐水、0.5 mg/L NETs和1.5 mg/L NETs处理尿道成纤维细胞,探索NETs对尿道成纤维细胞活化和胶原合成的影响。(3)构建尿道创伤新西兰兔模型,将动物分为非手术组、手术+转化生长因子β1(TGF-β1)注射(阳性对照)组、手术+生理盐水注射组和手术+脱氧核糖核酸酶I(DNase I)溶液注射组,探索NETs降解剂DNase I对尿道瘢痕形成的治疗作用。结果:尿道创伤后,患者尿液NETs水平显著升高(P<0.05),而血液NETs水平无显著差异(P>0.05)。尿道创伤新西兰兔模型中,创伤后尿液NETs水平越高,形成的尿道瘢痕纤维化程度越高(P<0.05);在细胞层面上,NETs促进尿道成纤维细胞活力、迁移与胶原合成(P<0.05)。在新西兰兔尿道创伤模型中,创伤后尿道注射DNase I可降低局部NETs水平,抑制尿道瘢痕形成(P<0.05)。结论:NETs浸润促进尿道创伤后尿道成纤维细胞活化和增生性瘢痕形成。AIM:This study was performed to investigate the impact of neutrophil extracellular traps(NETs)on scar formation following urethral trauma.METHODS:(1)Clinical samples were derived from patients of Department of Urology,The First Affiliated Hospital of Fujian Medical University,from June 2021 to December 2022.Levels of NETs in the blood and urine were compared between patients with urethral trauma(n=20)and those without urethral trauma(controls,n=20).The relationship between NETs and scar formation was analyzed.(2)Urethral fibroblasts were isolated from urethral scar tissues,and neutrophils were induced to produce NETs in vitro.The urethral fibroblasts were treated with normal saline,0.5 mg/L NETs,or 1.5 mg/L NETs to investigate the effects of NETs on activation and collagen synthesis of urethral fibroblasts.Additionally,a rabbit model of urethral trauma was established and the animals were dioided into four groups to explore the therapeutic potential of deoxyribonuclease I(DNase I)in preventing urethral scar formation:control,operation+transforming growth factor-β1(TGF-β1),operation+normal saline,and operation+DNase I.RESULTS:The level of NETs in urine increased after urethral trauma(P<0.05),but the level of NETs in blood did not change(P>0.05).In the animal models,the urethral scar became more severe as the level of NETs in the urine increased(P<0.05).At the cellular level,NETs promoted the viability,migration,and collagen synthesis of urethral fibroblasts(P<0.05)..Additionally,urethral injection of DNase I after trauma reduced the level of NETs and inhibited the formation of urethral scar tissue in the animal models(P<0.05).CONCLUSION:Infiltration of NETs promotes activation of urethral fibroblasts and scar formation after urethral trauma.

关 键 词：中性粒细胞胞外诱捕网 创伤后尿道狭窄 瘢痕形成 尿道成纤维细胞 

分 类 号：R695[医药卫生—泌尿科学] R363.2[医药卫生—外科学]