肝硬化门静脉高压症患者肠壁屏障功能的改变及其与易发感染的关系  

Changes of intestinal wall barrier function and its correlation with susceptibility to infection in patients with cirrhotic portal hypertension

作　　者：林晓宇[1] 李琛 张婷[1] 陈靖[1] 江家骥[1] 郑琦[1] Lin Xiaoyu;Li Chen;Zhang Ting;Chen Jing;Jiang Jiaji;Zheng Qi(Department of Hepatology,Hepatology Research Institute,the First Affiliated Hospital,Fujian Medical University,Fujian Clinical Research Center for Hepatology and Intestinal Diseases,Fuzhou 350005,China)

机构地区：[1]福建医科大学附属第一医院肝病中心、福建医科大学肝病研究所、福建省肝病与肠道疾病临床医学研究中心,福州350005

出　　处：《中华肝脏病杂志》2023年第1期70-76,共7页Chinese Journal of Hepatology

基　　金：福建省科技厅社会发展引导性(重点)项目(2019Y0014);福建医科大学启航基金项目(2018QH1052)。

摘　　要：目的探讨肝硬化门静脉高压症患者肠壁屏障功能的改变及与发生感染的相关性。方法收集263例肝硬化患者分为临床症状明显的门静脉高压(CEPH)并感染组(n=74);CEPH组(n=104);非CEPH组(n=85)。其中非感染状态的20例CEPH患者和12例非CEPH患者行乙状结肠黏膜活组织检查,免疫组织化学染色法检测结肠黏膜髓系细胞触发受体-1(TREM-1)、CD68、CD14、诱导型一氧化氮合酶分子和大肠杆菌(E.coli)表达。酶联免疫吸附法检测外周血炎症标志物可溶性髓系细胞触发受体-1(sTREM-1)、可溶性白细胞分化抗原-14亚型(sCD14-ST)与肠壁通透性指标肠型脂肪酸结合蛋白(I-FABP)水平。分别采用Fisher确切概率法、单因素方差分析、Kruskal-Wallis-H检验、Bonferroni法及Spearman相关分析等进行统计学分析。结果非感染状态下,CEPH患者血清sTREM-1、I-FABP水平高于非CEPH患者(P<0.05),而血sCD14-ST水平差异无统计学意义(P>0.05);CEPH患者中,并发感染患者的血清sTREM-1、sCD14-ST、I-FABP水平均高于未并发感染的患者(P<0.05)。血清sCD14-ST水平与血清sTREM-1、C反应蛋白(CRP)、降钙素原(PCT)呈正相关、sTREM-1水平与CRP、PCT亦呈正相关(r值均>0.5,P值均<0.001)。CEPH组的肠黏膜CD68、诱导型一氧化氮合酶、CD14阳性细胞率和E.coli阳性腺体率均高于对照组(P<0.05)。Spearman相关分析表明CEPH患者E.coli阳性腺体率与固有层巨噬细胞分子标志物CD68、CD14表达呈正相关。结论肝硬化合并门静脉高压患者肠壁通透性增加、炎症细胞增多伴随细菌移位,血清sCD14-ST和sTREM-1可作为预测和评估肝硬化合并门静脉高压症患者感染发生的指标。Objective To investigate the changes of intestinal wall barrier function and its correlation with infection occurrence in patients with cirrhotic portal hypertension.Methods 263 patients with cirrhotic portal hypertension were split into:the clinically evident portal hypertension(CEPH)combined with infection group(n=74);CEPH group(n=104);and Non-CEPH group(n=85).Among them,20 CEPH patients and 12 non-CEPH patients in non-infection status were subjected to sigmoidoscopy.Immunohistochemical staining was used to detect the expression of trigger receptor-1(TREM-1),CD68,CD14,the inducible nitric oxide synthase molecule,and Escherichia coli(E.coli)in the medullary cells of the colon mucosa.An enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of soluble myeloid cell trigger receptor-1(sTREM-1),soluble leukocyte differentiation antigen-14 subtype(sCD14-ST)and intestinal wall permeability index enteric fatty acid binding protein(I-FABP).Fisher’s exact probability method,one-way ANOVA,Kruskal-Wallis-H test,Bonferroni method,and Spearman correlation analysis were used for statistical analysis.Results The serum sTREM-1 and I-FABP levels were higher in CEPH patients than those of non-CEPH patients in the non-infectious state(P<0.05),but the difference in blood sCD14-ST levels was not statistically significant(P>0.05).Serum levels of sTREM-1,sCD14-ST,and I-FABP in infected patients were higher than those in patients without a concurrent infection(P<0.05).Serum sCD14-ST levels were positively correlated with serum sTREM-1,C-reactive protein(CRP),and procalcitonin(PCT),and sTREM-1 levels were also positively correlated with CRP and PCT(r>0.5,P<0.001).The rates of CD68,inducible nitric oxide synthase,CD14-positive cells,and E.coli-positive glands were higher in the intestinal mucosa of the CEPH group than those of the control group(P<0.05).Spearman’s correlation analysis showed that the rate of E.coli-positive glands in CEPH patients was positively correlated with the expression of molecular markers CD68 a

关 键 词：肝硬化 临床显著性门静脉高压 肠壁通透性 感染 巨噬细胞 

分 类 号：R575.2[医药卫生—消化系统]