不同阶段慢性乙型肝炎患者外周血单个核细胞中NF-κB/iNOS的表达及免疫状态

黄津; 张美泉; 何道兴

doi:10.3969/j.issn.1001-5256.2020.03.013

不同阶段慢性乙型肝炎患者外周血单个核细胞中NF-κB/iNOS的表达及免疫状态

DOI: 10.3969/j.issn.1001-5256.2020.03.013

1. 福建医科大学附属南平第一医院感染科
2. 福建省立医院北院感染科

基金项目:

福建省卫生计生委青年基金(2017-1-94)；

详细信息

中图分类号: R512.62
计量
- 文章访问数: 940
- HTML全文浏览量: 17
- PDF下载量: 219
- 被引次数: 0
出版历程
- 出版日期: 2020-03-20

Expression of nuclear factor-kappa B and inducible nitric oxide synthase in peripheral blood mononucleated cells and immune status in patients with different stages of chronic hepatitis B

Department of Infectious Diseases, Nanping First Hospital Affiliated to Fujian Medical University

Research funding:

摘要

摘要: 目的研究核因子-κB（NF-κB）/诱导型一氧化氮合成酶（iNOS）在不同阶段慢性乙型肝炎患者外周血单个核细胞（PBMC）中的表达,比较各阶段自然杀伤细胞及T、B淋巴细胞的变化情况。方法纳入福建医科大学附属南平第一医院2017年10月-2019年1月慢性乙型肝炎相关疾病患者,按照疾病不同阶段分4组:肝炎组、肝衰竭组、肝硬化组、肝癌组,每组各20例;另选取10例健康志愿者作为对照组。采用流式细胞仪检测5组外周血总淋巴细胞计数和淋巴细胞亚群计数;采用Western Blot检测PBMC中NF-κB、iNOS蛋白的表达水平;硝酸还原酶法和ELISA法检测血清中NO、IL-6水平。多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果与对照组比较,肝炎组、肝衰竭组、肝癌组、肝硬化组总淋巴细胞计数水平均明显下降（P值均<0. 05）;与肝炎组比较,肝衰竭组、肝癌组、肝硬化组总淋巴细胞计数水平均明显下降（P值均<0. 05）。肝衰竭组、肝癌组、肝硬化组CD3+明显下降,分别与对照组、肝炎组比较差异均有统计学意义（P值均<0. 05）;肝衰竭组、...
- 乙型肝炎,慢性 /
- NF-κB /
- 一氧化氮合酶 /
- 淋巴细胞
Abstract: Objective To investigate the expression of nuclear factor-kappa B( NF-κB) and inducible nitric oxide synthase( iNOS) in peripheral blood mononucleated cells( PBMCs) of patients with different stages of chronic hepatitis B( CHB),as well as the changes in natural killer( NK),T,and B lymphocytes in each stage. Methods A total of 80 patients with CHB-related diseases who were admitted to Nanping First Hospital Affiliated to Fujian Medical University from October 2017 to January 2019 were enrolled and divided into four groups according to disease stage: hepatitis group,liver failure group,liver cirrhosis group,and liver cancer group,with 20 patients in each group,and ten healthy volunteers were enrolled as control group. Flow cytometry was used to measure total lymphocyte count as well as the counts of lymphocyte subsets in peripheral blood in all five groups,Western blot was used to measure the protein expression of NF-κB and iNOS in PBMCs,and the nitrate reductase method and ELISA were used to measure the serum levels of nitric oxide( NO) and interleukin-6( IL-6). A one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups. Results Compared with the control group,the hepatitis group,the liver failure group,the liver cancer group,and the liver cirrhosis group had a significant reduction in total lymphocyte count( all P < 0. 05),and compared with the hepatitis group,the liver failure group,the liver cancer group,and the liver cirrhosis group had a significant reduction in total lymphocyte count( all P < 0. 05). The liver failure group,the liver cancer group,and the liver cirrhosis group had a significant reduction in CD3+T cells compared with the control group and the hepatitis group( all P < 0. 05),as well as a significant reduction in CD4+T cells compared with the hepatitis group( all P < 0. 05); the liver failure group had a significant increase in CD8+T cells compared with the liver cancer group,the liver cirrhosis group,and the control group( all P < 0. 05); the liver failure group had a significant reduction in CD4+/CD8+compared with the control group,the hepatitis group,the liver cirrhosis group,and the liver cancer group( all P < 0. 05); the liver failure group and the liver cirrhosis group had a significant increase in CD3-CD19+B cells compared with the hepatitis group and the control group( all P < 0.05); the liver failure group and the liver cancer group had a significant reduction in CD16+CD56+NK cells compared with the hepatitis group and the control group( all P < 0. 05). The liver cirrhosis group,the liver failure group,and the liver cancer group had significant increases in the protein expression of NF-κB and iNOS compared with the hepatitis group and the control group( all P < 0. 05). Compared with the control group,the liver failure group,the liver cancer group,the liver cirrhosis group,and the hepatitis group had significant increases in the serum levels of NO and IL-6( all P < 0. 05). Conclusion There are certain differences in immune status between patients with different stages of HBV infection,and NF-κB-iNOS-NO may be involved in the immune response of HBV-related diseases.
- hepatitis B,chronic /
- NF-kappa B /
- nitric oxide synthase /
- lymphocytes

HTML全文

参考文献(16)

[1] PAN CJ,WU HL,KUO SF,et al. Serum interleukin 6 level correlates with outcomes of acute exacerbation of chronic hepatitis B[J]. Hepatol Int,2012,6(3):591-597.

[2] HONG M,BERTOLETTI A. Tolerance and immunity to pathogens in early life:Insights from HBV infection[J]. Semin Immunopathol,2017,39(6):643-652.

[3] DU Z,DONG J,BI J,et al. Correction:Predictive value of the preoperative neutrophil-to-lymphocyte ratio for the development of hepatocellular carcinoma in HBV-associated cirrhotic patients after splenectomy[J]. PLo S One,2019,14(4):e0215183.

[4] Chinese Society of Hepatology and Chinese Society of Infectious Diseases,Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B:A 2015 update[J]. J Clin Hepatol,2015,31(12):1941-1960.(in Chinese)中华医学会肝病学分会，中华医学会感染病学分会．慢性乙型肝炎防治指南(2015年更新版)[J]．临床肝胆病杂志，2015,31(12):1941-1960.

[5] Liver Failure and Artificial Liver Group,Chinese Society of Infectious Diseases,Chinese Medical Association; Severe Liver Disease and Artificial Liver Group,Chinese Society of Hepatology,Chinese Medical Association. Guideline for diagnosis and treatment of liver failure(2018)[J]. J Clin Hepatol,2019,35(1):38-44.(in Chinese)中华医学会感染病学分会肝衰竭与人工肝学组，中华医学会肝病学分会重型肝病与人工肝学组．肝衰竭诊治指南(2018年版)[J]．临床肝胆病杂志，2019,35(1):38-44.

[6] SHI HM,LI R,CHEN H,et al. An excerpt of EASL clinical practice guidelines for the management of patients with decompensated cirrhosis(2018)[J]. J Clin Hepatol,2018,34(8):1632-1638.(in Chinese)史慧敏，李瑞，陈红，等．《2018年欧洲肝病学会失代偿期肝硬化患者的管理临床实践指南》摘译[J]．临床肝胆病杂志，2018,34(8):1632-1638.

[7] National Health and Family Planning Commission of the People's Republic of China. Diagnosis,management,and treatment of hepatocellular carcinoma(V2017)[J]. J Clin Hepatol,2017,33(8):1419-1431.(in Chinese)中华人民共和国国家卫生和计划生育委员会．原发性肝癌诊疗规范(2017年版)[J]．临床肝胆病杂志，2017,33(8):1419-1431.

[8] WANG Y,CHEN C,QI J,et al. Altered PGE2-EP2 is associated with an excessive immune response in HBV-related acute-on-chronic liver failure[J]. J Transl Med,2019,17(1):93.

[9] ZHANG W,ZHANG J,ZHAO L,et al. TIPE2 protein negatively regulates HBV-specific CD8+T lymphocyte functions in humans[J]. Mol Immunol,2015,64(1):204-209.

[10] GAO W,KONG M,YAO J,et al. Changes in prealbumin and body mass index associated with T lymphocyte subsets and nutritional status in chronic hepatitis B and HBV-cirrhosis patients[J]. Clin Lab,2018,64(11):180-184.

[11] SUN KK,HUANG CH,WANG YY,et al. Detection of T lymphocyte surface costimulatory molecules and T lym-phocyte subsets in peripheral blood of HBV infected patients and its clinical significance[J]. Chin J Clin Pharmacol Ther,2019,24(3):241-247.(in Chinese)孙凯凯，黄春红，王云云，等．HBV感染者外周血T淋巴细胞表面共刺激分子和T淋巴细胞亚群的检测及临床意义[J]．中国临床药理学与治疗学，2019,24(3):241-247.

[12] BAARDY F,MALMASSARI S,DENG Q,et al. Hepatitis B virus(HBV)-derived DRB1*0101-restricted CD4 T-cell epitopes help in the development of HBV-specific CD8+T cells in vivo[J]. Vaccine,2010,28(22):3818-3826.

[13] QI X,GUI X,ZHUANG K,et al. Establishment and characterization of HBV-associated B lymphocytes with an immortalization potential[J]. PLo S One,2019,14(5):e0217161.

[14] LIN J,GU C,SHEN Z,et al. Hepatocyte nuclear factor 1αdownregulates HBV gene expression and replication by activating the NF-κB signaling pathway[J]. PLo S One,2017,12(3):e0174017.

[15] SASAKI Y,IWAI K. Roles of the NF-κB pathway in B-lymphocyte biology[J]. Curr Top Microbiol Immunol,2016,393:177-209.

[16] MA XL,LI YH,GAO JX,et al. Effect and its'significance of NF-κB on inducible nitric oxide expression in concanavalin A induced immune liver injury[J]. J Shandong Univ(Health Sciences),2005,43(2):98-102.(in Chinese)马雪莲，李跃华，高建新，等．刀豆蛋白A诱导的肝损伤中核因子-κB对诱导型一氧化氮合酶表达的调控及其意义[J]．山东大学学报(医学版)，2005,43(2):98-102.

施引文献

资源附件(0)

访问统计