巨噬细胞极化及CXCL9水平与炎症性肠病进展和复发的相关性  

Correlation between macrophage polarization and CXCL9 and the progression and recurrence of inflammatory bowel disease

作　　者：孙晓睿 张津铭 李孝文 瞿斯文 方智芸 阙扬铭 刘潇钰 于牧鑫 沈海燕 SUN Xiaorui;ZHANG Jinming;LI Xiaowen;QU Siwen;FANG Zhiyun;QUE Yangming;LIU Xiaoyu;YUMuxin;SHEN Haiyan(Graduate School of Bengbu Medical University,Bengbu 233000,Anhui,China;Department of Gastroenterology,Second Affiliated Hospital of Jiaxing University,Jiaxing 314000,Zhejiang,China;Department of Pathology,Second Affiliated Hospital of Jiaxing University,Jiaxing 314000,Zhejiang,China;Medical College of Jiaxing University,Jiaxing 314000,Zhejiang,China)

机构地区：[1]蚌埠医科大学研究生院,蚌埠233000 [2]嘉兴大学附属第二医院消化内科,嘉兴314000 [3]嘉兴大学附属第二医院病理科,嘉兴314000 [4]嘉兴大学医学院,嘉兴314000

出　　处：《医学研究与战创伤救治》2024年第9期945-952,共8页Journal of Medical Research & Combat Trauma Care

基　　金：浙江省医药卫生科技计划项目(2021KY1116);嘉兴市科技计划项目(2022AD30007)。

摘　　要：目的探讨M1/M2型巨噬细胞比例以及CXCL9水平与炎症性肠病(IBD)进展及复发的相关性。方法选取2021年9月至2023年6月嘉兴大学附属第二医院收治的70例IBD患者作为研究对象。同期选取30例性别、年龄相匹配的体检人群作为对照。将其分为:对照、初发活动期、缓解期、复发活动期,利用酶联免疫吸附测定法检测4组血清样本中TNF-α、INOS、IL-6、IL-10、ARG-1、CXCL9水平进行比较,利用HE染色及组织免疫化学染色检测4组肠组织中炎症细胞浸润、M1型巨噬细胞特异性标志物抗体CD86、M2型巨噬细胞特异性标志物抗体CD206及趋化因子CXCL9并进行分析。Logistic回归分析受试者血清中的影响因素,血清INOS/ARG-1比值代表M1/M2型巨噬细胞比例,绘制不同指标对IBD进展与复发的受试者工作曲线;结果初发活动期及复发活动期M1型巨噬细胞相关的TNF-α、INOS、IL-6、IFN-γ细胞因子水平较对照及缓解期IBD明显升高(P<0.05);缓解期M2型巨噬细胞相关的ARG1、IL-10细胞因子水平较对照及初发及复发活动期IBD明显升高(P<0.05);与对照及缓解期IBD相比,初发及复发活动期M1/M2及CXCL9水平明显升高(P<0.05)。TNF-α、INOS、IL-6、IFN-γ、M1/M2、CXCL9是评估初发活动期IBD疾病活动度的影响因素(P<0.05)。ARG1、IL-10是评估缓解期IBD疾病活动度的影响因素(P<0.05)。TNF-α、INOS、IL-6、IFN-γ、M1/M2、CXCL9是评估复发活动期IBD疾病活动度的影响因素(P<0.05)。M1/M2联合CXCL9评估IBD疾病活动度的AUC为0.937(95%CI:0.891~0.982,P<0.05),根据约登指数最大原则,评估IBD疾病活动度的最佳临界值分别为2.410,396.57,此时其评估IBD疾病活动度的敏感度为91.4%,特异度为91.2%。结论M1/M2型巨噬细胞比例及CXCL9水平与IBD进展与复发具有相关性,对于评估IBD的疾病活动度具有一定的预测价值。Objective To explore the correlation between the ratio of M1/M2 macrophages and CXCL9 and the progression and recurrence of inflammatory bowel disease(IBD).Methods A total of 70 IBD patients admitted to the Second Hospital affiliated to Jiaxing University from September 2021 to June 2023 were selected.During the same period,30 gender and age-matched healthy individuals undergoing physical examinations were selected as controls.They were divided into the following groups:control,primary active,remission,and relapsed active.Serum samples from all four groups were tested and compared for TNF-α,INOS,IL-6,IL-10,ARG-1 and CXCL9 using enzyme-linked immunosorbent assay(ELISA).HE staining and immunohistochemistry were used to examine intestinal tissue infiltration by inflammatory cells,the specific markers for M1 macrophages(CD86),M2 macrophages(CD206)and the chemokine CXCL9 across the four groups.Logistic regression analysis was performed to identify influencing factors in the serum.The INOS/ARG-1 ratio represented the proportion of M1/M2 macrophages.Receiver operating characteristic(ROC)curves were plotted for different indicators to assess predictive values for IBD progression and recurrence.Results The levels of TNF-α,INOS,IL-6,IFN-γcytokines associated with M1 macrophages were significantly higher in the primary and relapsed active groups compared to the control and remission groups(P<0.05);The levels of ARG1 and IL-10 associated with M2 macrophages were significantly higher in the remission group compared to the control,primary and relapse active group(P<0.05);Compared to the control and remission group,the M1/M2 ratio and CXCL9 levels were significantly elevated in the primary and relapse active groups(P<0.05).TNF-α,INOS,IL-6,IFN-γ,M1/M2 ratio,and CXCL 9 were identified as influential factors for assessing disease activity in the primary active group(P<0.05).ARG 1 and IL-10 were influencing factors for assessing the disease activity of in the remission group(P<0.05).TNF-α,INOS,IL-6,IFN-γ,M1/M2 ratio,and CXCL

关 键 词：巨噬细胞极化 CXCL9 黏膜炎症 炎症性肠病 疾病活动度 

分 类 号：R574[医药卫生—消化系统]