中性粒细胞胞外诱捕网在原发性胆汁性胆管炎患者中的作用初步探析  

A preliminary study of the role of neutrophil extracellular traps in patients with primary biliary cholangitis

作　　者：偶绎颜 崔娜娜 李瑶 钱其炜 马雄[1] 尤征瑞[1] 连敏[1] 王绮夏[1] OU Yiyan;CUI Nana;LI Yao;QIAN Qiwei;MA Xiong;YOU Zhengrui;LIAN Min;WANG Qixia(Division of Gastroenterology and Hepatology,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai Institute of Digestive Disease,Shanghai 200001,China)

机构地区：[1]上海交通大学医学院附属仁济医院消化内科,上海市消化疾病研究所,上海200001

出　　处：《临床肝胆病杂志》2022年第4期810-814,共5页Journal of Clinical Hepatology

基　　金：国家自然科学基金项目(82070581,81800504,81770564,81790634);上海市教育委员会和上海市教育发展基金会“晨光计划”(19CG16);上海市卫生计生系统优秀青年医学人才培养计划(2017YQ037);上海市青年科技启明星计划(18QA1402700)。

摘　　要：目的探索原发性胆汁性胆管炎(PBC)患者外周血和肝组织内中性粒细胞胞外诱捕网(NET)表达水平,及其与临床生化指标的相关性。方法选取2016年8月—2020年8月上海交通大学医学院附属仁济医院收治的PBC患者24例、年龄匹配的原发性硬化性胆管炎(PSC)8例以及自身免疫性肝炎(AIH)患者19例、健康对照(HC)18例,分别检测血清中髓过氧化物酶(MPO)水平,并与临床指标进行相关性分析。利用组织免疫荧光检测PBC患者肝内NET表达情况。体外实验比较PBC患者和健康对照组外周血中性粒细胞产生NET能力的差异。满足正态分布的计量资料2组间比较采用独立样本t检验,非正态分布计量资料多组间比较采用Kruskal-Wallis H检验,2组间比较采用Mann-Whitney U检验。对MPO水平与肝脏相关实验室指标进行相关性分析,计算Spearman相关系数。结果PBC组血清中的MPO水平[811.21(450.67~1216.20)ng/mL]较AIH组[468.58(142.63~812.43)ng/mL]和HC组[357.54(203.52~811.21)ng/mL]明显升高(P值均<0.05);提示在PBC患者外周血中NET的产生量显著增加。PSC患者血清中MPO水平[763.56(489.59~1633.14)ng/mL]也较HC组显著升高(P<0.05)。MPO水平与ALP(r=0.500,P<0.05)、GGT(r=0.426,P<0.05)、ALT(r=0.521,P<0.01)和AST(r=0.547,P<0.01)水平之间存在正相关关系。免疫荧光共聚焦显示PBC患者肝内存在H3Cit、MPO共定位。体外实验观察到PBC患者外周血中性粒细胞较健康对照在体外刺激时产生NET增多,且自发产生NET亦增高。结论PBC患者外周血及肝内NET增多,且外周血NET的含量与肝功能生化指标呈正相关。NET或可成为评估疾病严重程度的新型生物学标志物。Objective To investigate the expression level of neutrophil extracellular traps(NET)in the peripheral blood and liver tissue of primary biliary cholangitis(PBC)patients and its correlation with clinical biochemical parameters.Methods A total of 24 PBC patients who were admitted to Renji Hospital,Shanghai Jiao Tong University School of Medicine,from August 2016 to August 2020 were enrolled,as well as 8 patients with primary sclerosing cholangitis(PSC)and 19 patients with autoimmune hepatitis(AIH)matched for age,and 19 healthy individuals were enrolled as healthy control group(HC group).The serum level of myeloperoxidase(MPO)was measured,and its correlation with clinical indices were analyzed.Immunofluorescence assay was used to measure the expression of NET in the liver of PBC patients,and an in vitro experiment was to compare the ability of peripheral blood neutrophils to produce NET between PBC patients and healthy controls.Normally distributed continuous data were expressed as mean±standard deviation,and the independent samples t-test was used for comparison between two groups;for the non-normally distributed continuous data expressed as M(P;-P;),the Kruskal-Wallis H test was used for comparison between multiple groups,and the Mann-Whitney U test was used for comparison between two groups.A correlation analysis was performed for MPO level and liver-related laboratory markers,and the Spearman’s correlation coefficient was calculated.Results The serum level of MPO in the PBC group was increased to 811.21(450.67-1216.20)ng/mL,which was significantly higher than that in the AIH group[468.58(142.63-812.43)ng/mL]and the HC group[357.54(203.52-811.21)ng/mL](P<0.05),suggesting that there was a significant increase in the production of NET in peripheral blood of PBC patients.The PSC patients had a serum MPO level of 763.56(489.59-1633.14)ng/mL,which was significantly higher than that in the HC group(P<0.05).MPO level was positively correlated with alkaline phosphatase(r=0.500,P<0.05),gamma-glutamyl transpeptidase(r=0

关 键 词：原发性胆汁性胆管炎 中性粒细胞 胞外诱捕网 

分 类 号：R575.7[医药卫生—消化系统]