丙型肝炎病毒感染不同临床转归患者Toll样受体及干扰素α表达变化  

Research on expression of Toll-like receptors and IFN-αin HCV infected patients with different clinical outcomes

作　　者：吴慕青 葛军 李昂 吴涛 WU Muqing;GE Jun;LI Ang;WU Tao(Hainan Affiliated Hospital of Hainan Medical University,Hainan General Hospital,Haikou,Hainan 570311,China)

机构地区：[1]海南医学院附属海南医院,海南省人民医院,海南海口570311

出　　处：《中国热带医学》2023年第10期1011-1016,共6页China Tropical Medicine

基　　金：国家自然科学基金项目(No.8186060246);海南省临床医学中心建设项目(琼卫医函[2021]276号);海南省高层次人才项目(No.2019RC371)。

摘　　要：目的研究直接抗病毒药物(direct-acting antiviral agents,DAAs)治疗丙型肝炎病毒(hepatitis C virus,HCV)感染不同临床转归患者Toll样受体(Toll like receptor,TLR)及干扰素α(interferonα,IFN-α)的表达变化情况,探索TLR3及IFN-α的表达水平与HCV临床转归的关系。方法选择2020年9月—2022年8月海南省人民医院门诊149例慢性HCV感染初治患者,分为慢性丙型肝炎(chronic hepatitis C,CHC)组129例和肝硬化(liver cirrhosis,LC)组20例,同期选择28名健康志愿者为对照组。所有HCV感染患者首次给予索磷布韦/维帕他韦片治疗12周,分别收集治疗基线0、4、12、24、48周血标本,采用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测肝功能指标,实时荧光定量聚合酶链反应(real-time polymerase chain reaction,qRCR)检测TLR3 mRNA的表达。Luminex多细胞因子检测IFN-α的表达。比较不同组别间差异。结果TLR3 mRNA在CHC组中基线时高表达于LC组及对照组(P<0.05)。经DAAs治疗4周后、CHC组及LC组TLR3 mRNA显著上调(P<0.05)。CHC组在12、24、48周中TLR3 mRNA表达可逐渐下调至对照组水平。此外,IFN-α在CHC组中随治疗时间延长表达逐渐上调,在LC组中表达下调。CHC组及LC组肝脏炎症指标经DAAs治疗后可部分恢复。结论TLR3参与病毒清除及慢性炎症反应,经DAAs治疗后,在HCV感染不同临床转归患者中TLR3的表达差异可能与疾病的严重程度有关。Objective To investigate the changes in expression of Toll-like receptor 3(TLR3)and interferon-α(IFN-α)in patients with different clinical outcomes of hepatitis C virus(HCV)infection treated with direct-acting antiviral agents(DAAs),and to explore the relationship between the expression of TLR3 and IFN-αwith the clinical outcomes of HCV infection.Methods A total of 149 HCV infected patients who received initial treatment were selected from Hainan General Hospital between September 2020 and August 2022.The patients were divided into two groups:chronic hepatitis C(CHC)group(n=129)and liver cirrhosis(LC)group(n=20).Additionally,28 volunteers were selected as the control group during the same period.All patients with HCV infection were first treated with Sofosbuvir/Vipatavir tablets for 12 weeks.Blood samples were collected at 0,4,12,24 and 48 weeks after treatment.Liver function indicators were detected by enzyme-linked immunosorbent assay(ELISA),while TLR3 mRNA were detected by real-time fluorescence quantitative polymerase chain reaction(qRCR),IFN-αwas detected by Luminex multiplex cytokine assays.Measurement data subject to normal distribution were represented by x±s,and t test was used between groups.Compare differences between groups.Results TLR3 mRNA in CHC group was higher than that in LC group and control group at baseline(P<0.05).After 4 weeks of DAAs treatment,TLR3 mRNA in CHC and LC groups was significantly up-regulated(P<0.05).TLR3 mRNA in the CHC group was gradually downregulated to the level of the control group at 12,24,and 48 weeks.In addition,IFN-αexpression gradually increased with prolonged treatment,while it decreased in the LC group.The liver inflammation indicators in both the CHC and LC groups partially recovered after treatment with DAAs.Conclusions TLR3 is involved in viral clearance and chronic inflammatory response.The expression difference of TLR3 in patients with different clinical outcomes of HCV infection after DAAs treatment may be related to the severity of the disease.

关 键 词：慢性丙型肝炎病毒 直接抗病毒药物 TOLL样受体 干扰素Α 

分 类 号：R373.21[医药卫生—病原生物学]