肝脏CD4^(+)T细胞、IL-6、IL-8、IL-33的表达与术后胆管炎及黄疸清除的关系研究  

Relationship between the expressions of CD4^(+)T cells,IL-6,IL-8 and IL-33 in liver and postoperative cholangitis and jaundice clearance

作　　者：章开智 陈雨彤 郑泽兵 汤成艳 祝代威 夏兴容 黄露 杜青 刘远梅 金祝 Zhang Kaizhi;Chen Yutong;Zheng Zebing;Tang Chengyan;Zhu Daiwei;Xia Xingrong;Huang Lu;Du Qing;Liu Yuanmei;Jin Zhu(Department of Pediatric Surgery,Affiliated Hospital of Zunyi Medical University Guizhou Children's Hospital,Zunyi 563000,China)

机构地区：[1]遵义医科大学附属医院小儿外科,贵州省儿童医院小儿外科,遵义563000

出　　处：《中华小儿外科杂志》2022年第12期1088-1094,共7页Chinese Journal of Pediatric Surgery

基　　金：国家自然科学基金(81760099);遵市科合HZ字((2019)104号)。

摘　　要：目的检测胆道闭锁(biliary atresia,BA)患儿肝组织中CD4^(+)T细胞和炎症因子IL-6、IL-8、IL-33的表达水平,并探讨其与术后胆管炎及早期退黄之间的关系。方法选取2018年6月至2020年5月遵义医科大学附属医院收治的29例BA患儿和16例先天性胆管扩张症(congenital biliary dilatation,CBD)患儿的肝脏标本。HE染色及免疫组织化学检测CD4^(+)T细胞、IL-6、IL-8、IL-33的表达及分布。记录BA患儿术前、术后1周、2周及3个月总胆红素(total bilirubin,TBIL)水平和胆管炎发生情况,根据胆管炎发生情况分为胆管炎、无胆管炎、早期胆管炎、晚期胆管炎、频发胆管炎和偶发胆管炎。分析比较BA患儿肝脏炎症水平与术后胆管炎的发生及黄疸清除之间的关系。结果HE染色结果显示BA患儿肝脏汇管区浸润着大量炎症细胞,伴肝内胆汁淤积、小胆管增生以及肝细胞水肿,CBD患儿肝组织汇管区见轻度炎症细胞浸润。免疫组织化学染色结果显示BA患儿中CD4^(+)T细胞、IL-6、IL-8、IL-33表达水平高于CBD患儿。ROC曲线分析显示,CD4^(+)T细胞、IL-6和IL-8的平均光密度值鉴别BA与CBD的曲线下面积分别为0.869、0.886和0.838。胆管炎患儿CD4^(+)T细胞、IL-6、IL-8表达水平高于无胆管炎患儿,早期胆管炎患儿CD4^(+)T细胞表达水平高于晚期胆管炎患儿,频发胆管炎患儿CD4^(+)T细胞、IL-6、IL-8、IL-33表达水平稍高于偶发胆管炎患儿。BA患儿CD4^(+)T细胞表达水平与术后3个月TBIL下降率呈负相关(r=-0.532,P=0.034),IL-8和IL-33表达水平与术后1周TBIL下降率呈负相关(r=-0.384,P=0.048;r=-0.568,P=0.002)。结论BA患儿肝脏组织中CD4^(+)T细胞、IL-6、IL-8及IL-33高表达,可能易发胆管炎。CD4^(+)T细胞、IL-8、IL-33表达水平越高,早期黄疸清除率越低,可作为早期黄疸清除率的预测指标。Objective To detect the expression levels of CD4^(+)T cells and IL-6/8/33 in liver tissue of biliary atresia(BA)and to examine the relationship between the expression levels and postoperative cholangitis and early yellowing.Methods From June 2018 to May 2020,liver samples were collected from 29 BA and 16 congenital biliary dilatation(CBD)children.Hematoxylin-eosin(HE)stain and immunohistochemistry were employed for detecting the expressions and distributions of CD4^(+)T cells,IL-6/8/33.Total bilirubin level and occurrence of cholangitis in BA group were recorded preoperatively,1 week,2 weeks and 3 months postoperatively.According to the occurrence of cholangitis,BA group was divided into six groups of cholangitis,non-cholangitis,early cholangitis,late cholangitis,frequent cholangitis and occasional cholangitis.The relationship was analyzed between BA liver inflammation and postoperative cholangitis and jaundice clearance.Results HE staining indicated that a heavy infiltration of inflammatory cells in hepatic portal area of BA group,accompanied by intrahepatic cholestasis,a proliferation of small bile ducts and hepatic cell edema.A milder infiltration of inflammatory cells was present in hepatic portal area of CBD group.Immunohistochemical staining indicated that the expressions of CD4^(+)T cells,IL-6,IL-8 and IL-33 were higher in BA group than those in CBD group.Receiver operating characteristic(ROC)curve showed that area under the curve of CD4^(+)T cells,IL6 and IL8 was 0.869,0.886 and 0.838 respectively.The expression levels of CD4^(+)T cells,IL-6 and IL-8 in cholangitis group were higher than that in non-cholangitis group;the expression level of CD4^(+)T cells was higher in early cholangitis group than that in late cholangitis group.And the expression levels of CD4^(+)T cells,IL-6,IL-8 and IL-33 were slightly higher in frequent cholangitis group than those in occasional cholangitis group.The expression level of CD4^(+)T cells in BA group was negatively correlated with total bilirubin(TBIL)declining rate at Mon

关 键 词：胆道闭锁 炎症细胞 炎症因子 胆红素 胆管炎 

分 类 号：R726.5[医药卫生—儿科]