慢性乙型肝炎和肝硬化患者血清TLR4、TGF-β1和IL-17水平及其临床意义*

doi:10.3969/j.issn.1672-5069.2018.04.024

摘要/Abstract

摘要： 目的分析慢性乙型肝炎（CHB）和乙型肝炎肝硬化患者血清Toll样受体4（TLR4）、转化生长因子-β1（TGF-β1）和白细胞介素-17（IL-17）水平变化及其临床意义。方法 2015年6月~2017年4月本院收治的112例CHB、52例乙型肝炎肝硬化患者和选择的33例健康人,采用ELISA法检验血清IL-17、TLR4、TGF-β1水平,常规进行肝活检。结果慢性乙型肝炎、肝硬化和健康人血清IL-17水平分别为（264.42±32.53） pg/ml、（271.54±33.71） pg/ml和（64.18±5.52） ng/ml,血清TLR4水平分别为（5.81±0.83） pg/ml、（37.41±6.05） pg/ml和（1.07±0.13）ng/ml,血清TGF-β1水平分别为（3.67±0.42） pg/ml、（7.82±1.07） pg/ml和（1.61±0.07） ng/ml,差异明显（P<0.05）;19例Child-Pugh B级血清IL-17、TLR4和TGF-β1水平分别为（231.38±28.67） pg/ml、（18.61±2.87） pg/ml和（5.76±0.52） ng/ml,16例C级患者分别为（301.72±32.72） pg/ml、（39.47±6.82） pg/ml和（9.42±1.27） ng/ml,均明显高于17例Child-Pugh A级患者【分别为（204.53±26.57） pg/ml、（4.72±0.71） pg/ml和（3.18±0.34） ng/ml,P<0.05】;肝活检组织学检查发现S0 8例、S1 42例、S2 43例、S3 19例、S4 52例,血清IL-17、TLR4、TGF-β1水平随着肝组织纤维化分期严重而升高。结论乙型肝炎肝硬化患者血清TLR4、TGF-β1和IL-17水平升高,对诊断和指导治疗可能有帮助。

关键词: 慢性乙型肝炎, 肝硬化, Toll样受体4, 转化生长因子-β, 1, 白细胞介素-17

Abstract: Objective To investigate serum levels of Toll like receptor 4（TLR4）,transforming growth factor beta 1（TGF-β1） and interleukin-17 （IL-17） in patients with chronic hepatitis B （CHB） and hepatitis B-induced liver cirrhosis. Methods 112 patients with CHB,52 patients with hepatitis B liver cirrhosis and 33 healthy persons in our hospital between June 2015 and April 2017 were enrolled in this study. Serum IL-17, TLR4 and TGF-β1 levels were detected by enzyme linked immunosorbent assay （ELISA） and liver biopsy was performed routinely. Results Serum levels of IL-17 in patients with chronic hepatitis B,liver cirrhosis and healthy persons were（264.42±32.53） pg/ml,（271.54±33.71） pg/ml and （64.18±5.52） ng/ml,respectively,serum levels of TLR4 were （5.81±0.83） pg/ml,（37.41±6.05） pg/ml and （1.07±0.13） ng/ml respectively, and serum levels of TGF-β1 were （3.67±0.42） pg/ml,（7.82±1.07） pg/ml and （1.61±0.07） ng/ml, respectively （P<0.05）;serum IL-17,TLR4 and TGF-β1 levels in 19 patients with Child-Pugh class B were（231.38±28.67） pg/ml,（18.61±2.87）pg/ml and （5.76±0.52） ng/ml,in 16 patients with class C were（301.72±32.72） pg/ml,（39.47±6.82） pg/ml and （9.42±1.27） ng/ml,both were significantly higher than in 17 patients with Child-Pugh class A【（204.53±26.57） pg/ml,（4.72±0.71） pg/ml and（3.18±0.34）ng/ml,respectively,P<0.05】;the liver biopsies showed than liver fibrosis staging So in 8,S1 in 42,S2 in 43,S3 in 19 and S4 in 52. Serum IL-17,TLR4 and TGF-β1 levels in each group of liver fibrosis were significantly different（P<0.05）,and they increased as the pathological fibrosis stages got worse. Conclusion Serum levels of TLR4,TGF-β1 and IL-17 increase in patients with CHB and hepatitis B-induced liver cirrhosis,which might hint the diagnosis and the severity of liver cirrhosis.

Key words: Hepatitis B, Liver cirrhosis, Toll like receptor 4, Transforming growth factor beta 1, Interleukin-17

赵秀娟, 金大鹏, 张小云, 刘泽林, 孙向华. 慢性乙型肝炎和肝硬化患者血清TLR4、TGF-β1和IL-17水平及其临床意义^*[J]. 实用肝脏病杂志, 2018, 21(4): 581-584.

Zhao Xiujuan, Jin Dapeng, Zhang Xiaoyun, et al. Serum TLR4,TGF-β1 and IL-17 levels in patients with chronic hepatitis B and hepatitis B-induced liver cirrhosis[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(4): 581-584.

参考文献

[1] Lemmers A,Moreno C,Gustot T,et al.The interleukin-17 pathway is involved in human alcoholic liver disease. Hepatology,2009,49(2):646-657.
[2] Fujimoto M,Uemura M,Nakatani Y et al. Plasma endotoxin and serum cytokine levels in patients with alcoholic hepatitis:relation to severity of liver disturbance.Alcohol Clin Exp Res,2000,24(4 Suppl):48S-54S.
[3] Glāssner A,Eisenhardt M,Kokordelis P,et al.Impaired CD4+ T cell stimulation of NK cell anti-fibrotic activity may contribute to accelerated liver fibrosis progression in HIV/HCV patients. J Hepatol,2013,59(3):427-433.
[4] He X,Hong Y,Wang X,et al.Identification and clinical significance of an elevated level of serum aminoacylase-1 autoanti-body in patients with hepatitis B virus-related liver cirrhosis. Mol Med Rep,2016,14(5):4255.
[5] 中华医学会肝病学分会和感染病学分会.慢性乙型肝炎防治指南(2015年版).实用肝脏病杂志,2016,19(3):Ⅴ-ⅩⅩⅢ.
[6] 李彩东,杨勇卫,田鹏飞,等. 慢性乙型肝炎病毒感染者血清MIF、IL-17和IL-10水平变化. 实用肝脏病杂志,2015,18(1):71-73.
[7] Sun HQ,Zhang JY,Zhang H,et al.Increased Th17 cells contribute to disease progression in patients with HBV-associated liver cirrhosis.J Viral Hepat,2012,19(6):396-403.
[8] 曾波,李彦. 慢性乙型肝炎和肝硬化患者血清骨桥蛋白和TGF-β1水平变化. 实用肝脏病杂志,2017,20(2):152-164.
[9] Buechler C,Schiffler A,Johann M,et al.Elevated adiponectin serum levels in patients with chronic alcohol abuse rapidly decline during alcohol withdrawal.J Gastroenterol Hepatol,2009,24(4):558-563.
[10] Lee P L,Chen J J,Tung H D,et al.Serum hepatitis B surface antigen level might predict cirrhosis and hepatocellular carcinoma in older patients with chronic hepatitis B. Adv Dig Med,2015,2(3):102-107.
[11] Jurczyk K,Wawrzynowicz M,Boroń A,et al.Serum iron parameters in patients with alcoholic and chronic cirrhosis and hepatitis.Med Sci Monit,2001,7(5):962-965.
[12] 庄权权,林志航,蒋燕成,等. 慢性乙型肝炎病毒感染患者血清免疫调节因子检测的临床意义. 中华医院感染学杂志,2016,26(1):1-3.
[13] Taeb J,Mathurin P,Elbim C,et al.Blood neutrophil functions and cytokine release in severe alcoholic hepatitis:effect of corticosteroids.J Hepatol,2000,32(4):579-586.
[14] Elefsiniotis IS,Skounakis M,Vezali E,et al.Clinical significance of serum procalcitonin levels in patients with acute or chronic liver disease.Eur J Gastroenterol Hepatol,2006,18(5):525-530.
[15] Kawakami Y,Nabeshima S,Furusyo N,et al.Increased frequency of interferon-gamma-producing peripheral blood CD4+T cells in chronic hepatitis C virus infection.Am J Gastroenterol,2000,95(1):227-232.
[16] 周扬梅,李宁,黄燕,等. 慢性重型乙型肝炎患者血清 Slit2蛋白的临床意义. 中国感染控制杂志,2015,14(11):726-729.
[17] Vecchiet J,Falasca K,Cacciatore P,et al.Association between plasma interleukin-18 levels and liver injury in chronic hepatitis C virus infection and non-alcoholic fatty liver disease.Ann Clin Lab Sci,2005,35(4):415-422.
[18] Mukhopadhyay P,Saha S,Philips CA,et al.Clinical, biochemical and pathological correlation in alcoholic liver disease among Indian patients.Trop Gastroenterol,2012,33(3):218-220.
[19] Papp M,Sipeki N,Vitalis Z,et al.High prevalence of IgA class anti-neutrophil cytoplasmic antibodies (ANCA) is associated with increased risk of bacterial infection in patients with cirrhosis. J Hepatol,2013,59(3):457-466.
[20] Dominguez M,Miquel R,Colmenero J,et al.Hepatic expression of CXC chemokines predicts portal hypertension and survival in patients with alcoholic hepatitis.Gastroenterology,2009,136(5):1639-1650.
[21] Wu LY,Liu S,Liu Y,et al.Up-regulation of interleukin-22 mediates liver fibrosis via activating hepatic stellate cells in patients with hepatitis C.Clin Immunol,2015,158(1):77-87.
[22] Aceti A,Mangoni ML,Pasquazzi C,et al.Alpha-defensin increase in peripheral blood mononuclear cells from patients with hepatitis C virus chronic infection.J Viral Hepat,2006,13(12):821-827.
[23] Eggers V,Pascher A,Althoff H,et al.Immune reactivity is more suppressed in patients with alcoholic liver disease than in patients with virus-induced cirrhosis after CRH stimulation.Alcohol Clin Exp Res,2006,30(1):140-149.
[24] Degré D,Lemmers A,Gustot T,et al.Hepatic expression of CCL2 in alcoholic liver disease is associated with disease severity and neutrophil infiltrates.Clin Exp Immunol,2012,169(3):302-310.
[25] 陈轶,陈益耀,韩向阳,等. 幽门螺杆菌与乙型肝炎病毒对乙型病毒性肝炎患者胃黏膜病变的相关分析. 中华医院感染学杂志,2016,26(14):3184-3186.
[26] 魏卓,杨广民,陈晶. 慢性乙型肝炎及其相关肝硬化、肝癌患者肝组织中TLR4、TGF-β1及CCL20的表达及意义. 广东医学,2016,37(5):684-688.
[27] 郑吉顺,陈萌萌,周翔天,等. 白细胞介素-17在慢性乙型肝炎及肝硬化患者中的表达及意义比较. 中国临床药理学杂志,2016,32(6):495-498.
[28] 张婷,马丹旭,李晞等. 原发性胆汁性肝硬化不同分期中Th17细胞及转化生长因子-β1的水平差异.中华风湿病学杂志,2015,19(8):507-511.
[29] 孙丽,李红胜,阮玲娟,等. 慢性乙型肝炎患者外周血辅助性T细胞9及白细胞介素9的表达及临床意义. 疾病监测,2015,30(1):35-37.
[30] 黄国栋,谢艺琴,杨碧新,等. 慢性乙型肝炎患者血清TGF-β_1水平及其与肝纤维化的相关性研究. 海南医学,2015,28(13):1890-1891.
[31] 邵丽春,邓国伟,金国贤. 慢性乙型肝炎外周血单个核细胞与血清中TOⅡ样受体及Th1/Th2/Th17型细胞因子的表达. 中国临床医生杂志,2016,38(11):39-42.
[32] 林江,王珂,陈孙云. 自身免疫性肝病和病毒性肝炎患者血清中抗肝抗体检测的临床意义. 现代检验医学杂志,2015,41(3):153-156.
[33] 张菁,崔剑巍,成伟忠,等. 基于“伏邪”说的肝复安治疗慢性乙型肝炎患者铁代谢异常临床观察. 上海中医药杂志,2016,18(8):38-42.
[34] 范宸颖,覃小梅,彭慧云,等. 儿童乙型病毒性肝炎肝脏病理与肝功能、肝纤维化血清学指标的关系. 医学临床研究,2016,33(3):543-545.
[35] 李成德,蔡健梅,吴小文,等. 乙型肝炎患者血清B7-H3和IFN-γ的水平及临床意义. 细胞与分子免疫学杂志,2015,31(11):1533-1536.

慢性乙型肝炎和肝硬化患者血清TLR4、TGF-β1和IL-17水平及其临床意义^*

Serum TLR4,TGF-β1 and IL-17 levels in patients with chronic hepatitis B and hepatitis B-induced liver cirrhosis

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	庄莹, 林志辉. 肝硬化并发门静脉血栓临床表现和诊断进展[J]. 实用肝脏病杂志, 2019, 22(6): 765-767.
[2]	朱凌云, 张茂海, 崔莎莎, 张秋萍. 慢性乙型肝炎患者血清IL-12、IL-18水平和外周血单个核细胞FOXp3基因水平研究^*[J]. 实用肝脏病杂志, 2019, 22(6): 816-819.
[3]	石莹莹, 王元喜. 替比夫定联合阿德福韦酯治疗慢性乙型肝炎患者效果及其对肾功能的影响^*[J]. 实用肝脏病杂志, 2019, 22(6): 820-823.
[4]	闵峰, 黄文琪, 吴卫兵, 张丽, 范荣华. 慢性乙型肝炎患者血清脂肪细胞因子水平变化及其临床意义^*[J]. 实用肝脏病杂志, 2019, 22(6): 824-827.
[5]	张迎明, 申爽, 田飞, 孙园园. IFNL4和IL-28B基因多态性检测评估慢性乙型肝炎患者抗病毒治疗应答价值分析^*[J]. 实用肝脏病杂志, 2019, 22(6): 828-831.
[6]	潘美民, 李文娟, 蒋芳清, 杨丽晖, 谭永卫, 何娟, 阮建文, 蔡春琳. 慢性丙型肝炎患者血清IL-17A、FGF和IL-7水平与丙型肝炎病毒感染自发清除临床意义探讨^*[J]. 实用肝脏病杂志, 2019, 22(6): 840-843.
[7]	汪道伟, 方坚, 范凌. 自身免疫性肝炎患者血清IL-21和趋化因子水平变化及其临床意义探讨^*[J]. 实用肝脏病杂志, 2019, 22(6): 844-847.
[8]	杨才勇, 陈娜, 李奎, 江自成, 卜蓉蓉. 慢性丙型肝炎和丙型肝炎肝硬化患者外周血Treg和Th17水平变化临床意义探讨^*[J]. 实用肝脏病杂志, 2019, 22(6): 868-871.
[9]	朱娅鸽, 刘锦峰. 丁二磺酸腺苷蛋氨酸联合复方甘草酸苷治疗酒精性肝硬化患者疗效及其对血清BGP水平的影响^*[J]. 实用肝脏病杂志, 2019, 22(6): 872-875.
[10]	武丹, 马向鹰. 非酒精性脂肪性肝病肝硬化患者胰岛素抵抗水平与颈动脉硬化程度和左心室功能研究^*[J]. 实用肝脏病杂志, 2019, 22(6): 876-879.
[11]	陈梅梅, 段晓燕, 曹海霞, 丁雯瑾. 复方鳖甲软肝片治疗原发性胆汁性肝硬化患者疗效分析^*[J]. 实用肝脏病杂志, 2019, 22(6): 880-883.
[12]	刘李, 杨烈, 陈海洋, 何承俊, 王建宇, 陈廷昊. 肝硬化门静脉高压症并发脾动脉盗血综合征患者脾切除联合贲门周围血管离断术后门脉血流动力学的变化^*[J]. 实用肝脏病杂志, 2019, 22(6): 884-887.
[13]	何志安, 余丽萍, 赖江琼, 黄思付. ARFI评估肝硬化并发食管胃底静脉曲张患者出血和门静脉血栓的价值分析^*[J]. 实用肝脏病杂志, 2019, 22(6): 888-891.
[14]	张燕妮, 孙晓花, 何海燕, 杜芸芸, 韩慧. 腔镜肝门肠吻合术治疗新生儿胆道闭锁症疗效初步研究^*[J]. 实用肝脏病杂志, 2019, 22(6): 920-923.
[15]	李传杰, 徐静, 王亮亮, 潘劲劲, 刘波. 恩替卡韦治疗慢性乙型肝炎患者血清HBsAg变化与病毒学应答的相关性研究[J]. 实用肝脏病杂志, 2019, 22(6): 928-929.