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山东大学学报(医学版) ›› 2016, Vol. 54 ›› Issue (7): 38-42.doi: 10.6040/j.issn.1671-7554.0.2015.828

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慢性HBV感染者外周血单个核细胞凋亡相关因子的表达及其与乙肝慢性化的关系

张琨,张孝国,崔杏杏,陈士俊   

  1. 济南市传染病医院肝病科, 山东 济南 250021
  • 收稿日期:2015-09-01 出版日期:2016-07-10 发布日期:2016-07-10
  • 通讯作者: 陈士俊. E-mail:csj7516@sina.com E-mail:csj7516@sina.com

Expression of apoptosis-related genes in peripheral blood mononuclear cells of patients with HBV infection and the relationship with chronicity of hepatitis B

ZHANG Kun, ZHAGN Xiaoguo, CUI Xingxing, CHEN Shijun   

  1. The Department of Liver Diseases, Jinan Infectious Hospital, Jinan 250021, Shandong, China
  • Received:2015-09-01 Online:2016-07-10 Published:2016-07-10

摘要: 目的 探讨外周血淋巴细胞凋亡的不同路径及其在HBV感染慢性化过程中的作用。 方法 应用实时荧光定量PCR对9例慢性HBV携带者(ASC组),48例慢性乙型肝炎患者(CHB组),24例肝硬化(LC组)患者和20例正常对照者(NC组)外周血单个核细胞(PBMC)中的凋亡相关基因(FAS、CASP8、CYCS、CASP9、CASP3)进行检测,同时应用酶联免疫吸附试验(ELISA)检测血浆中的凋亡相关基因在蛋白水平的表达。 结果 CHB组和ASC组PBMC中凋亡相关基因mRNA水平的表达较NC组和LC组明显升高(P<0.05),CHB组和ASC组间差异无统计学意义(P>0.05),LC组高于NC组(P<0.05); CHB组和ASC组血浆中凋亡相关基因蛋白水平的表达较NC组和LC组明显升高(P<0.008 3),CHB组和ASC组间差异无统计学意义(P>0.008 3),LC组表达量较NC组升高(P<0.008 3)。 结论 HBV感染可诱导外周血单个核细胞凋亡,内源性路径和外源性路径均参与其中,PBMC的凋亡在HBV感染慢性化过程中发挥了重要作用。

关键词: 肝硬化, 外周血单个核细胞, 实时荧光定量PCR, 凋亡相关基因, 酶联免疫吸附试验, 慢性乙型肝炎

Abstract: Objective To investigate the different apoptosis pathways of peripheral blood lymphocytes cells(PBMCs)and their roles in the chronicity of HBV infection. Methods The study included 9 chronic asymptomatic HBV carriers(ASC), 48 patients with chronic hepatitis B(CHB), 24 patients with liver cirrhosis(LC)and 20 normal controls(NC). The mRNA expressions of apoptosis-related genes(FAS、CASP8、CYCS、CASP9、CASP3)in PBMCs were examined with real time fluorescent quantitative PCR, and the protein expressions in plasma were detected with enzyme linked immunosorbent assay(ELISA). Results The mRNA expressions of apoptosis-related genes were higher in CHB and ASC groups, as compared to NC and LC groups(P<0.05); there was no difference between CHB group and ASC group(P>0.05); the expressions were higher in LC group than in NC group(P<0.05). The protein expressions of apoptosis-related genes in CHB and ASC groups were higher than in NC and LC groups(P<0.008 3); there was no difference between CHB and ASC groups(P>0.008 3); the expressions were higher in LC group than in NC group(P<0.008 3). Conclusions HBV infection can induce the apoptosis of PBMCs, with extrinsic and intrinsic pathways involved. The apoptosis of PBMCs plays an important role in the chronicity of HBV infection.

Key words: Chronic hepatitis B, Peripheral blood mononuclear cell, Apoptosis-related gene, Cirrhosis, Enzyme linked immunosorbent assay, Real time quantitative PCR

中图分类号: 

  • R511
[1] 贾继东, 李兰娟. 慢性乙型肝炎防治指南(2010年版)[J]. 临床肝胆病杂志, 2011, 27(1): 113-128. JIA Jidong, LI Lanjuan. The guideline of prevention and treatment for chronic hepatitis B(2010 version)[J]. Clini Hepatol, 2011, 27(1): 113-128.
[2] 纪翠霞,胡九东,邢练军, 等. 乙型肝炎慢性化机制的研究现状[J]. 临床肝胆病杂志, 2012, 28(2): 149-152, 160. JI Cuixia, HU Jiudong, XING Lianjun, et al. Research on pathogenetic mechanism of chronic hepatitis B[J]. Clini Hepatol, 2012, 28(2): 149-152, 160.
[3] 李俊卿, 周俊英. 免疫细胞在慢性乙型肝炎免疫耐受机制中的作用[J]. 临床肝胆病杂志, 2011, 27(4): 437-440. LI Junqing, ZHOU Junying. The role of immune cells in immune tolerance mechanisms towards chronic hepatitis B[J]. Clini Hepatol, 2011, 27(4): 437-440.
[4] 邢同京, 章廉, 骆抗先, 等. 可活化诱导的淋巴细胞凋亡在乙型肝炎慢性化机制中的作用[J]. 中华传染病杂志, 2000, 18(4): 12-14. XING Tongjing, ZHANG Lian, LUO Kangxian, et al. Role of activation induced apoptosis of lymphocytes in the persistence of hepatitis B virus infection[J]. Chin J Infect Dis, 2000, 18(4): 12-14.
[5] Hou CS, Wang GQ, Lu SL, et al. Role of actination induced cell death in pathogenesis of patients with chronic hepatitis B[J]. World J Gastroenterol, 2003, 9(10): 2356-2358.
[6] Kumar S. Caspase function in programmed cell death[J]. Cell Death Differ, 2007, 14(1): 32-43.
[7] Szegezdi E, Logue SE, Gorman AM, et al. Mediators of endoplasmic reticulum stress-induced apoptosis[J]. EMBO Rep,2006,7(9):880-885.
[8] Basu A, Sato K, Meyer K, et al. Stellate cell apoptosis by a soluble mediator from immortalized human hepatocytes[J]. Apoptosis, 2006, 11(8): 1391-1400.
[9] Brenne C, Grimm S. The permeability transition pore complex in cancer cell death[J]. Oncogene, 2006, 25(34): 4744-4756.
[10] Green DR, Droin N, Pinkoski M. Activation-induced cell death in T cells[J]. Immunol Rev, 2003, 193: 70-81.
[11] Zhang J, Xu X, Liu Y. Activation-induced cell death in T cells and autoimmunity[J]. Cell Mol Immunol, 2004, 1(3): 186-192.
[12] 李玲, 顾长海, 李欣. 激活诱导细胞死亡在乙型肝炎发病机制中的意义[J]. 中华医学杂志, 2003, 83(13): 1146-1149. LI Ling, GU Changhai, LI Xin. The significance of activation-induced cell death(AICD)in pathogenesis of hepatitis B[J]. Nat Med J China, 2003, 83(13): 1146-1149.
[13] 吴克俭,颜学兵, 许统俭, 等. 慢性乙型肝炎、肝硬化患者外周血淋巴细胞CD95的表达及意义[J]. 徐州医学院学报, 2002, 22(2): 101-103. WU Kejian, YAN Xuebing, XU Tongjian, et al. Expression of CD95 in peripheral blood lymphocytes of patients with hepatitis B and liver cirrhosis[J]. ACTA ACADEMIAE MEDICINAE XUZHOU, 2002, 22(2): 101-103.
[14] Cao D. Intrahepatic expression of programmed death-1 and its ligands in patients with HBV-related acute-on-chronic liver failure[J]. Inflammation, 2013, 36(1): 110-120.
[15] Karev VE. Fas, FasL, and bcl-2 expression on hepatic intralobar lymphocytes in different variants of the natural course of chronic HBV and HCV infection and in its outcomes[J]. Arkh Patol, 2014, 76(1): 16-21.
[16] 王海燕, 王来栓. 细胞凋亡通路研究进展[J]. 国外医学·生理、病理科学与临床分册, 2003, 23(5): 490-492. WANG Haiyan, WANG Laishuan. Research on cell apoptosis pathway[J]. Foreign Medical Sciences, Section of Pathophysiology and Clinical Medicine, 2003, 23(5): 490-492.
[17] Wang K. Autophagy and apoptosis in liver injury[J]. Cell Cycle, 2015, 14(11): 1631-1642.
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