原发性胆汁性胆管炎患者肝组织中自然杀伤细胞活化性受体及其配体的表达及意义  

Expression and clinical significance of the NK cell-activating receptor NKG2D and its ligand in liver tissue of patients with primary biliary cholangitis

作　　者：余海燕 韦进香 付海艳 杨依娜 涂荣芳 唐映梅[1] YU Haiyan;WEI Jinxiang;FU Haiyan;YANG Yina;TU Rongfang;TANG Yingmei(Department of Gastroenterology,The Second Affiliated Hospital of Kunming Medical University,Kunming 650101,China)

机构地区：[1]昆明医科大学第二附属医院消化内科,昆明650101

出　　处：《临床肝胆病杂志》2020年第11期2456-2461,共6页Journal of Clinical Hepatology

基　　金：国家自然科学基金(81660102,81360072);云南省自然科学基金(2018FE001-051,2013FB050)。

摘　　要：目的探讨原发性胆汁性胆管炎(PBC)中NK细胞活化性受体(NKG2D)及其配体(MICA)、相关细胞因子(IFNγ、IL-10、IL-15)表达与肝内炎症的关系。方法选取2014年8月-2015年6月在昆明医科大学第二附属医院住院且确诊为PBC(PBC组,n=30)、慢性乙型肝炎(CHB组,n=15)和非酒精性脂肪性肝病(NAFLD组,n=10)患者的肝穿刺活检标本。判断肝脏标本的肝脏炎症活动度(G)和纤维化程度(S),采用免疫组化法分别观察3组肝组织中NKG2D、MICA、IFNγ、IL-10、IL-15的表达情况(根据染色细胞多少及染色深浅计算染色评分,判断各指标表达情况)。计量资料多组间比较采用单因素方差分析,两组间比较采用t检验,相关性分析采用Spearman分析。结果 PBC组NKG2D的表达随炎症程度加重而上升,G3~4级者明显高于G1~2级者(G1vs G2 vs G3 vs G4:1.4±0.05 vs 1.56±0.05 vs 1.86±0.11 vs 2.60±0.17,F=150.8,P <0.05);随纤维化程度加重而下降(S3 vs S4:2.30±0.17 vs 1.56±0.05,t=-1.52,P <0.05)。PBC组G3与G4级MICA比较差异无统计学意义(0.11±0.01 vs 0.20±0.03,t=-2.20,P> 0.05),S3与S4级比较差异无统计学意义(0.12±0.02 vs 0.18±0.03,t=-2.64,P> 0.05)。PBC组IL-15在炎症程度组间比较差异有统计学意义(G1 vs G2 vs G3 vs G4:0.70±0.10 vs 1.50±0.10 vs 1.93±0.11 vs 2.60±0.17,F=251.3,P <0.05),在纤维化程度组间比较差异无统计学意义(S3 vs S4:2.00±0.05 vs 2.40±0.30,t=-1.62,P> 0.05)。CHB组IL-15的表达在不同炎症程度组间比较差异有统计学意义(G1 vs G2 vs G3:0.73±0.15 vs 1.96±0.15 vs 2.50±0.17,F=150,P <0.05),在不同纤维化程度组间比较差异有统计学意义(S1 vs S2 vs S3:0.70±0.10 vs 21.96±0.15 vs 2.50±0.17,F=158.7,P <0.05)。PBC组IL-10仅G1期表达(0.16±0.01),CHB组G1、G2级均表达IL-10,且差异无统计学意义(G1 vs G2:0.19±0.01 vs 0.13±0.01,t=-1.522,P> 0.05)。PBC患者肝组织IL-15的表达与ALP、GGT水平均呈正相关(r值分别为0.241、0.407,P值分别为0.014、0.045)。结论 NK细�Objective To investigate the association of the expression of the NK cell-activating receptor NKG2D,its ligand major histocompatibility complex class I chain-related gene A(MICA),and related cytokines[interferon-γ(IFN-γ),interleukin-10(IL-10),and interleukin-15(IL-15)]with intrahepatic inflammation in primary biliary cholangitis(PBC).Methods Liver biopsy specimens were collected from 30 patients with PBC(PBC group),15 patients with chronic hepatitis B(CHB group),and 10 patients with nonalcoholic fatty liver disease(NAFLD group),who were hospitalized in The Second Affiliated Hospital of Kunming Medical University from August 2014 to June 2015.The degree of liver inflammation(G)and fibrosis degree(S)of the liver specimens were determined,and immunohistochemistry was used to measure the expression of NKG2D,MICA,IFN-γ,IL-10,and IL-15 in liver tissue(the scores were determined based on the number of cells stained and the degree of staining to evaluate the expression of each marker).A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the t-test was used for comparison between two groups;a Spearman correlation analysis was used to investigate correlation.Results In the PBC group,the expression of NKG2D increased with the degree of inflammation,and the patients with G3-4 inflammation had significantly higher expression than those with G1-2 inflammation(G1 vs G2 vs G3 vs G4:1.4±0.05 vs 1.56±0.05 vs 1.86±0.11 vs 2.60±0.17,F=150.8,P<0.05);the expression of NKG2D decreased with fibrosis degree(S3 vs S4:2.30±0.17 vs 1.56±0.05,t=-1.52,P<0.05).In the PBC group,there was no significant difference in MICA between G3 and G4(0.11±0.01 vs 0.20±0.03,t=-2.20,P>0.05)and between S3 and S4(0.12±0.02 vs 0.18±0.03,t=-2.64,P>0.05).In the PBC group,there was a significant difference in the expression of IL-15 between the patients with different degrees of inflammation(G1 vs G2 vs G3 vs G4:0.70±0.10 vs 1.50±0.10 vs 1.93±0.11 vs 2.60±0.17,F=251.3,P<0.05),while there was no sign

关 键 词：原发性胆汁性胆管炎 NK细胞凝集素样受体亚家族K 细胞因子类 

分 类 号：R575.7[医药卫生—消化系统]