文章摘要
邵昱璋,严敏,胡妮,王海荣,付婷,高洁,张磊.母源外周血和胎盘组织中Toll样受体9表达在HBV宫内传播中的作用[J].中华流行病学杂志,2019,40(9):1065-1070
母源外周血和胎盘组织中Toll样受体9表达在HBV宫内传播中的作用
Role of TLR 9 expression in maternal peripheral blood and placenta in intrauterine transmission of HBV
投稿时间:2019-02-01  
DOI:10.3760/cma.j.issn.0254-6450.2019.09.009
中文关键词: 乙型肝炎病毒;Toll样受体9;宫内传播;显性感染;隐匿性感染
英文关键词: HBV;TLR 9;Intrauterine transmission;Dominate infection;Occult infection
基金项目:国家自然科学基金(81102140,81472988,81373058);国家重点研发计划(2016YFC1303204);陕西省重点研发计划(2018SF-166)
作者单位E-mail
邵昱璋 西安交通大学医学院 710061  
严敏 空军军医大学军事预防医学系流行病学教研室 特殊作业环境危害评估与防治教育部重点实验室, 西安 710032  
胡妮 空军军医大学军事预防医学系流行病学教研室 特殊作业环境危害评估与防治教育部重点实验室, 西安 710032  
王海荣 空军军医大学军事预防医学系流行病学教研室 特殊作业环境危害评估与防治教育部重点实验室, 西安 710032  
付婷 空军军医大学军事预防医学系流行病学教研室 特殊作业环境危害评估与防治教育部重点实验室, 西安 710032  
高洁 空军军医大学军事预防医学系流行病学教研室 特殊作业环境危害评估与防治教育部重点实验室, 西安 710032  
张磊 空军军医大学军事预防医学系流行病学教研室 特殊作业环境危害评估与防治教育部重点实验室, 西安 710032 drzhanglei@fmmu.edu.cn 
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中文摘要:
      目的 探讨Toll样受体9(TLR 9)经血液和胎盘途径在HBV宫内传播(BIT)中的作用。方法 对陕西省西北妇女儿童医院分娩的290例HBsAg阳性产妇为病例组和45例健康产妇为对照组进行流行病学调查, ELISA法检测产妇及子代外周血乙型肝炎(乙肝)五项和TLR 9水平,实时荧光定量PCR检测HBV DNA水平;免疫组织化学法检测TLR 9在胎盘组织中的表达。采用病例对照研究方法分析发生BIT的HBsAg阳性产妇TLR 9水平差异。结果 HBsAg阳性产妇所生新生儿发生HBV宫内显性感染(DBI)率、宫内隐匿性感染(OBI)率和BIT率分别为9.28%(27/291)、40.21%(117/291)和49.48%(144/291)。HBsAg阳性产妇及未传播组(NBIT)和OBI组的TLR 9水平均显著低于对照组(P<0.001),DBI组的TLR 9水平显著高于NBIT组和OBI组(P=0.000); OBI组中HBeAg阴性组的TLR 9水平显著低于HBeAg阳性组(P=0.01);HBV DNA载量分层中均随着BIT程度的加重,产妇外周血TLR 9含量明显增加(P<0.05);抗病毒治疗、注射免疫球蛋白和未接种乙肝疫苗组,均随着BIT程度的加重,产妇外周血TLR 9含量明显增加(P<0.05);DBI的胎盘组织中TLR 9表达显著高于OBI组和NBIT组(P<0.05)。结论 HBV一定程度下会抑制产妇体内分泌TLR 9,但HBeAg能刺激母体TLR 9分泌,随着BIT程度的加重,其体内TLR 9水平呈增高的组内交叉分化现象,因此,TLR 9不是一个能独立筛选分组的标记,但可以做为HBsAg阳性产妇监测管理的参考指标。
英文摘要:
      Objective To explore the role of TLR 9 in intrauterine transmission of hepatitis B virus (HBV) through blood pathway and placenta. Methods Epidemiological investigation was carried out in 290 HBsAg positive parturients and 45 normal parturients (control group) in Northwest Women and Children Hospital of Shaanxi Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect five serological makers of hepatitis B and TLR 9 levels in peripheral blood of pregnant women and newborns. HBV DNA was detected by real-time fluorescence quantitative PCR. Detection of TLR 9 expression in placenta by immunohistochemical method. A case-control study was conducted to analyze the difference of TLR 9 levels in placenta and peripheral blood of HBsAg-positive pregnant women with intrauterine transmission of HBV. Results The incidence of dominant HBV infection (DBI), occult HBV infection (OBI) and intrauterine transmission of HBV were 9.28% (27/291), 40.21% (117/291) and 49.48% (144/291) respectively. (1) The level of TLR 9 in peripheral blood of HBsAg-positive parturients, non-HBV intrauterine transmission (NBIT) group and OBI group were significantly lower than that of control group (P<0.001). The level of TLR 9 in DBI group was significantly higher than those in NBIT group and OBI group (P=0.000). (2) The TLR 9 level in HBeAg-negative group was significantly lower than that in HBeAg-positive parturients in OBI group (P=0.01). (3) With the increased severity of intrauterine transmission of HBV in each HBV DNA load group, the TLR 9 level in maternal peripheral blood increased significantly (P<0.05). (4) With the increased severity of intrauterine transmission of HBV, the levels of TLR 9 increased significantly in antiviral therapy, immunoglobulin injection and non-hepatitis B vaccine groups (P<0.05). (5) The expression of TLR 9 in placenta tissues with DBI group was significantly higher than that in OBI group and NBIT group (P<0.05). Conclusions HBV can inhibit the secretion of TLR 9 in parturient to some extent, but HBeAg can stimulate the secretion of TLR 9. However, with the increased severity of intrauterine transmission of HBV, the level of TLR 9 in parturients is increased by intra-group cross-differentiation. Therefore, TLR 9 is not an independent marker for screening and grouping, but it can be used as an reference indicator for the monitoring and management of HBsAg-positive parturients.
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