髓源性抑制细胞在胆道闭锁患儿中的表达及其临床意义  

Expression levels of myeloid-derived suppressor cells in children with biliary atresia and its clinical significance

作　　者：张梦欣 马俊妮 张茜 李康 曹国庆[1] 汤绍涛[1] Zhang Mengxin;Ma Junni;Zhang Xi;Li Kang;Cao Guoqing;Tang Shaotao(Department of Pediatric Surgery,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China)

机构地区：[1]华中科技大学同济医学院附属协和医院小儿外科,武汉430022

出　　处：《中华实验外科杂志》2024年第12期2821-2824,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金(82371718)。

摘　　要：目的探讨髓源性抑制细胞(MDSCs)在胆道闭锁(BA)外周血和肝组织中表达及其与肝门空肠吻合手术(HPE)预后的相关性。方法回顾性分析2021年1月至2023年9月在武汉协和医院小儿外科收治的30例胆道闭锁患儿(BA组)和24例对照组患儿。采用流式细胞术检测两组患儿外周血中MDSCs表型和比例, 以及产生的精氨酸酶1(ARG-1)活性和诱导型一氧化氮合成酶(iNOS)水平的变化。随后, 评估两组患儿肝组织MDSCs表达及其与炎症及纤维化分级的相关性, 以及外周血MDSCs与HPE术预后的关系。使用独立样本t检验分析组间差异和Spearman检验分析变量间相关性。结果与对照组患儿比较, BA组外周血中MDSCs(HLA-DR-CD33+CD11b+)水平高于对照组[(34.85±1.35)%比(15.50±5.20)%, t=6.238, P<0.05], 且MDSCs产生ARG-1和iNOS高于对照组[(8 823.33±376.34) MFI比(5 633.33±500.83) MFI, t=-8.820, P<0.001;(9 623.33±851.25) MFI比(6 310.00±511.18) MFI, t=-5.780, P<0.01]。BA组肝脏组织中MDSCs比例高于对照组[(4.90±0.93)%比(0.60±0.06)%, t=8.029, P<0.01], 升高的细胞亚群主要是单核细胞样MDSCs(HLA-DR-CD33+CD11b+CD14+CD15-)[(38.73±1.65)%比(1.77±0.12)%, t=38.69, P<0.001], 且BA组肝组织中CD33+和CD11b+细胞数量与汇管区炎症(r=0.517、0.567, P<0.05)和肝纤维化分级(r=0.506、0.521, P<0.05)存在显著相关性。HPE术后1年, 自体肝存活患者外周血MDSCs的ARG-1和iNOS水平高于非自体肝存活患者[(2 380.00±280.00) MFI比(1 626.67±166.23) MFI, t=-4.007, P<0.05;(4 066.67±435.58) MFI比(3 156.67±190.09) MFI, t=-3.316, P<0.05]。结论 BA患儿外周血和肝组织中MDSCs呈高表达, 术后1年自体肝存活率与MDSCs免疫抑制功能密切相关。ObjectiveTo investigate the expression levels of myeloid-derived suppressor cells(MDSCs)in peripheral blood and liver and their correlation with the prognosis of patients with biliary atresia(BA)after Kasai hepatic portoenterostomy(HPE).MethodsA retrospective analysis was performed on 30 patients with BA(BA group)and 24 patients in control group at Department of Pediatric Surgery,Wuhan Union Hospital between January 2021 and September 2023 were retrospectively analyzed,including 30 patients who underwent Kasai surgery in BA group and 24 choledochal cysts patients in control group.Flow cytometry was used to detect the phenotype and proportion of MDSCs in the peripheral blood of two groups prior to surgery,as well as changes in arginase 1(ARG-1)activity and inducible nitric oxide synthase(iNOS)levels.Subsequently,the MDSCs expression levels in liver tissue and its correlation with the inflammation grade and fibrosis stage,as well as the relationship between MDSCs in peripheral blood and postoperative prognosis were evaluated.Independent sample t test was used to analyze the inter-group differences and Spearman test was used to analyze the correlation between variables.ResultsThe MDSCs(HLA-DR-CD33+CD11b+)level in peripheral blood of BA group was significantly higher than that of control group[(34.85±1.35)%vs.(15.50±5.20)%,t=6.238,P<0.05],and the ARG-1 activity and iNOS levels produced by MDSCs in BA group were significantly higher than those of control group[(8823.33±376.34)MFI vs.(5633.33±500.83)MFI,t=-8.820,P<0.001;(9623.33±851.25)MFI vs.(6310.00±511.18)MFI,t=-5.780,P<0.01].The proportion of MDSCs in liver tissues of BA group was significantly higher than that of control group[(4.90±0.93)%vs.(0.60±0.06)%,t=8.029,P<0.01],among which the upregulated subset was mainly monocytic MDSCs(HLA-DR-CD33+CD11b+CD14+CD15-)[(38.73±1.65)%vs.(1.77±0.12)%,t=38.69,P<0.001].Moreover,the number of CD33+and CD11b+cells in liver tissue of BA patients were significantly associated with portal inflammation(r=0.517,0.567,P<0.05)

关 键 词：胆道闭锁 髓源性抑制细胞 自体肝存活 病理特征 

分 类 号：R726.5[医药卫生—儿科]