CAJ | 학술논문

目的探讨Th17细胞在慢性乙型肝炎(CHB)及其重症化中的变化.方法收集CHB患者32例(CHB组)、HBV相关慢加急性肝功能衰竭(ACLF)患者44例(ACLF组)及健康对照者20名(健康对照组).应用流式细胞术检测外周血Th17细胞频率,实时荧光定量PCR检测外周血单个核细胞( PBMC)中IL-17 mRNA表达,免疫组织化学检测肝组织内IL-17+细胞表达,ELISA检测血清IL-17水平,并动态观察不同预后ACLF患者血清IL-17水平变化趋势.正态分布数据采用方差分析,非正态数据采用Kruskal-Wallis H检验或U检验.结果 CHB、ACLF和健康对照组外周血PBMC中Th17细胞频率分别为(1.47±0.60)％、(3.20±1.08)％和(0.86±0.43)％；IL-17mRNA分别为4.32±1.77、18.32±8.21和1.00;肝组织内IL-17+细胞分别为(10.6±4.8)、(21.1±6.6)和(0.5±0.2)/高倍视野；血清IL-17分别为(15.88±6.51)、(35.03±11.54)和(10.04±4.06)ng/L(均P＜0.05).中晚期ACLF患者外周血Th17细胞频率和血清IL-17水平均高于早期ACLF患者(均P＜o.01).ACLF患者外周血Th17细胞频率与国际标准化比值(r=0.44.P＜0.01)和终末期肝病模型评分(r=0.44,P＜0.01)均呈正相关,丽CHB患者外周血Th17细胞频率与ALT水平呈正相关(r=0.51,P＜0.01).另外,ACLF存活患者血清IL-17基线水平低于死亡患者,且经内科治疗后逐渐下降,而死亡患者逐渐升高.结论 Th17细胞与其分泌的细胞因子IL-17可能促进了CHB肝脏损伤及其HBV相关ACLF的发生和发展,并且其水平越高可能预示患者短期预后越差.
목적 탐토Th17세포재만성을형간염(CHB)급기중증화중적변화.방법 수집CHB환자32례(CHB조)、HBV상관만가급성간공능쇠갈(ACLF)환자44례(ACLF조)급건강대조자20명(건강대조조).응용류식세포술검측외주혈Th17세포빈솔,실시형광정량PCR검측외주혈단개핵세포( PBMC)중IL-17 mRNA표체,면역조직화학검측간조직내IL-17+세포표체,ELISA검측혈청IL-17수평,병동태관찰불동예후ACLF환자혈청IL-17수평변화추세.정태분포수거채용방차분석,비정태수거채용Kruskal-Wallis H검험혹U검험.결과 CHB、ACLF화건강대조조외주혈PBMC중Th17세포빈솔분별위(1.47±0.60)％、(3.20±1.08)％화(0.86±0.43)％；IL-17mRNA분별위4.32±1.77、18.32±8.21화1.00;간조직내IL-17+세포분별위(10.6±4.8)、(21.1±6.6)화(0.5±0.2)/고배시야；혈청IL-17분별위(15.88±6.51)、(35.03±11.54)화(10.04±4.06)ng/L(균P＜0.05).중만기ACLF환자외주혈Th17세포빈솔화혈청IL-17수평균고우조기ACLF환자(균P＜o.01).ACLF환자외주혈Th17세포빈솔여국제표준화비치(r=0.44.P＜0.01)화종말기간병모형평분(r=0.44,P＜0.01)균정정상관,려CHB환자외주혈Th17세포빈솔여ALT수평정정상관(r=0.51,P＜0.01).령외,ACLF존활환자혈청IL-17기선수평저우사망환자,차경내과치료후축점하강,이사망환자축점승고.결론 Th17세포여기분비적세포인자IL-17가능촉진료CHB간장손상급기HBV상관ACLF적발생화발전,병차기수평월고가능예시환자단기예후월차.
Objective To explore the changes of Th17 cells in the pathogenesis and aggravation of chronic hepatitis B (CHB).Methods Thirty-two CHB patients,44 hepatitis B virus (HBV)related acute-on-chronic liver [ailure (ACLF) patients and 20 healthy controls (HC) were involved in our research. The frequencies of circulating Th17 cells were detected by flow cyrometry. The interleukin 17 (IL-17) mRNA expressions in the peripheral blood mononuclear cells (PBMC) were detected by quantitative real-time polymerase chain reaction (PCR).Immunohistochemical staining was performed to determine the expressions of IL-17+ cells in the liver tissues.The serum IL-17 concentrations were detected by enzyme-linked immunosorhent assay (ELISA),and the dynamic changes in ACLF patients with different prognosis were also observed.Normal distribution data were used by analysis of variance and non-normal distribution data were used by Kruskal-Wallis H test or Mann-Whitney U test.Results In CHB,ACLF and healthy control groups,Th17 cells frequencies in PBMC were (1.47 ± 0.60) ％,(3.20 ± 1.08) ％ and (0.86 ± 0.43) ％,respectively ; IL-17 mRNA were 4.32±11.77,18.32±8.21 and 1.00,respectively; IL-17+ cells in the liver tissues were (10.6±4.8),(21.1±6.6) and (0.5±0.2)/high power field; the level of IL-17 in serum were (15.88±6.51),(35.03±11.54) and (10.04±4.06) ng/L,respectively (all P＜0.05).Moreover,the frequencies of circulating Th17 cells and the levels of serum IL-17 in medium-stage and end-stage ACLF patients were higher than that in early-stage ACLF patients (both P ＜ 0.01). In ACLF patients,the circulating Th17 cells frequencies were positively correlated with international normalized ratio (INR,r=0.44,P＜0.01) and model of end-stage liver disease (MELD) score (r=0.44,P＜0.01).And the frequencies of circulating Th17 cells were positively associated with the serum alanine transaminase (ALT) levels in CHB patients (r=0.51,P＜0.01).Moreover,the survival ACLF patients had an initially lower serum IL-17 level compared with the non-survivors,and the serum IL-17 level showed a gradually decreasing trend during the course of medical treatment.In contrast,the nonsurvival group exhibited a gradually increasing trend.Conclusions Th17 cell and its cytokine IL-17 may contribute to liver injury in the pathogenesis of CHB and promote the occurrence and the development of HBV-related ACLF. Moreover,the elevated levels of Th17 cells and IL-17 may indicate poor short-term prognosis in ACLF patients.