[1]邹晶晶,朱小飞,余　杨.高危型人乳头状瘤病毒载量和Th1/Th2不均衡表达对宫颈病变进程的影响[J].新乡医学院学报,2019,36(11):1055-1059.[doi:10.7683/xxyxyxb.2019.11.012]
　ZOU Jing-jing,ZHU Xiao-fei,YU Yang.Effect of high risk human papillomavirus load and the unbalanced expression of Th1/Th2 type cytokines on the progression of cervical lesions[J].Journal of Xinxiang Medical University,2019,36(11):1055-1059.[doi:10.7683/xxyxyxb.2019.11.012]
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高危型人乳头状瘤病毒载量和Th1/Th2不均衡表达对宫颈病变进程的影响
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
36
期数:
2019年11
页码:
1055-1059
栏目:
临床研究
出版日期:
2019-11-05

文章信息/Info

Title:
Effect of high risk human papillomavirus load and the unbalanced expression of Th1/Th2 type cytokines on the progression of cervical lesions
作者:
邹晶晶1; 朱小飞2; 余　杨1
（1.焦作市第二人民医院检验科，河南　焦作　454150；2.新乡医学院分子诊断与医学检验技术河南省协同创新中心，河南　新乡　453003)
Author(s):
ZOU Jing-jing1; ZHU Xiao-fei2; YU Yang1
（1.Department of Laboratory，the Second People′s Hospital of Jiaozuo，Jiaozuo 454150，Henan Province，China；2.Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine,Xinxiang Medical University，Xinxiang 453003，Henan Province,China）
关键词:
宫颈局部免疫微环境; 宫颈病变; Th1/Th2细胞因子; 高危型人乳头状瘤病毒
Keywords:
local immune microenvironment of cervix; cervical carcinogenesis; Th1/Th2 type cytokines; high risk human papillomavirus
分类号:
R711.32
DOI:
10.7683/xxyxyxb.2019.11.012
文献标志码:
A
摘要:
目的　比较高危型人乳头状瘤病毒（HR-HPV）载量、Th1和Th2型细胞因子在不同病变宫颈组织中的表达，并分析其与宫颈病变进程的相关性。方法　将焦作市第二人民医院2012年1月至2015年9月收治的339例HR-HPV持续性感染的不同宫颈病变患者分为宫颈上皮内瘤变(CIN) Ⅰ组（n=71）、CIN Ⅱ组（n=66）、CIN Ⅲ组（n=77）和宫颈癌组（n=125），另选择人乳头状瘤病毒（HPV）阴性且细胞学检查为正常宫颈的40例健康体检者作为对照组。采用聚合酶链反应荧光法检测受试者宫颈分泌物中HR-HPV DNA水平，双抗体夹心酶联免疫吸附试验检测受试者宫颈灌洗液中Th1型细胞因子［白细胞介素（IL）-2、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）］和Th2型细胞因子（IL-4、IL-6、IL-10）水平，并以TNF-α/IL-10比值作为衡量Th1/Th2免疫平衡的指标，采用多元线性回归分析HR-HPV DNA与6种细胞因子的关系。结果　CIN Ⅱ组和CIN Ⅲ组患者宫颈分泌物中HR-HPV DNA载量比较差异无统计学意义（P>0.05），其余各组患者宫颈分泌物中HR-HPV DNA载量两两比较差异均有统计学意义（P<0.05）。CIN I组、CIN Ⅱ组、CIN Ⅲ组及宫颈癌组患者宫颈灌洗液中IL-2、IFN-γ、TNF-α、IL-4、IL-6、IL-10水平均高于对照组（P<0.05）。CIN I组、CIN Ⅱ组、CIN Ⅲ组及宫颈癌组患者宫颈灌洗液中IL-2、IFN-γ、TNF-α水平呈逐渐降低趋势，IL-4、IL-6、IL-10水平呈逐渐升高趋势;其中CIN Ⅱ组和CIN Ⅲ组患者宫颈灌洗液中IFN-γ、TNF-α、IL-4、IL-6水平比较差异无统计学意义（P>0.05）,其余各宫颈病变组两两比较差异均有统计学意义（P<0.05）；各宫颈病变组患者宫颈灌洗液中IL-2、IL-10水平两两比较差异均有统计学意义（P<0.05）。对照组、CIN I组、CIN Ⅱ组TNF-α/IL-10比值比较差异均无统计学意义（P>0.05）；CIN Ⅲ组、宫颈癌组患者TNF-α/IL-10比值显著小于对照组、CIN I组、CIN Ⅱ组（P<0.05）；宫颈癌组患者TNF-α/IL-10比值小于CIN Ⅲ组（P<0.05）。多元线性回归分析显示,IL-2、IL-4水平与HR-HPV DNA载量无线性关系（P>0.05）；IL-6、IL-10、IFN-γ、TNF-α水平与HR-HPV DNA载量存在线性关系（P<0.05），与HR-HPV载量的密切程度依次为IL-10>IL-6>IFN-γ>TNF-α。结论　CIN至宫颈癌进程中，其局部微环境中细胞因子逐渐向Th2方向偏移，最终导致Th1/Th2失衡，局部免疫失衡可能是HR-HPV持续性感染和宫颈癌变的关键环节。
Abstract:
Objective　To compare the difference of high risk human papillomavirus(HR-HPV) DNA load and the Th1/Th2 type cytokines levels in different cervical lesions tissue and analyze the correlation between them and the process of cervical lesions.Methods　Three hundred and thirty-nine HR-HPV persistent infection cervical lesions patients admitted to the Second People′s Hospital of Jiaozuo from January 2012 to September 2015 were divided into cervical intraepithelial neoplasia(CIN) I group (n=71),CIN Ⅱ Group (n=66),CIN Ⅲ group (n=77) and cervical cancer group (n=125).Forty healthy people with negative human papillomavirus (HPV) infection and normal cervix confirmed by cytology were selected as control group.The levels of HR-HPV DNA in cervical secretions of all subjects were detected by polymerase chain reaction;the levels of Th1 cytokines ［interleukin(IL)-2,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α) ］and Th2 cytokines (IL-4,IL-6,IL-10) in cervical lavage fluid of all subjects were detected by double antibody sandwich enzyme-linked immunosorbent assay;the ratio of Th1/Th2 was used to measure immune balance;the relationship between HR-HPV DNA load and six cytokines was analyzed by multiple linear regression.Results　There was no significant difference in the HR-HPV DNA load of patients between CIN Ⅱ group and CIN Ⅲ group (P>0.05);there was statistic difference in the HR-HPV DNA load of patients among the other cervical lesions groups(P<0.05).The levels of IL-2,IFN-γ,TNF-α,IL-4,IL-6 and IL-10 in cervical lavage fluid of patients in the CIN I group,CIN Ⅱ group,CIN Ⅲ group and cervical cancer group were significantly higher than those in the control group (P< 0.05).The levels of IL-2,IFN-γ and TNF-α in cervical lavage fluid of patients in the CIN I group,CIN Ⅱ group,CIN Ⅲ group and cervical cancer group decreased gradually,while the levels of IL-4,IL-6 and IL-10 increased gradually.There was no significant difference in the levels of IFN-γ,TNF-α,IL-4 and IL-6 in cervical lavage fluid of patients between the CIN Ⅱ group and the CIN Ⅲ group (P>0.05),but there was significant difference in another cervical lesions groups (P< 0.05);there was significant difference in the levels of IL-2 and IL-10 in cervical lavage fluid of patients between all the cervical lesions groups (P< 0.05).There was no significant difference in the ratio of TNF-α/IL-10 among the control group,CIN I group,CIN Ⅱ group(P>0.05);the ratio of TNF-α/IL-10 of patients in CIN Ⅲ group and cervical cancer group was significantly lower than that in the control group,CIN I group and CIN Ⅱ group (P<0.05);the ratio of TNF-α/IL-10 of patients in cervical cancer group was significantly lower than that in the CIN Ⅲ group (P<0.05).Multivariate linear regression analysis showed that there was no linear relationship between IL-2,IL-4 levels and HR-HPV DNA load(P> 0.05)；there was a linear relationship between IL-6,IL-10,IFN-γ,TNF-α levels and HR-HPV DNA load (P<0.05),and the degree of closeness with HR-HPV DNA was IL-10>IL-6>IFN-γ>TNF-α.Conclusion　In the process of CIN to cervical cancer,the cytokine in the local microenvironment gradually shift to Th2,which led to the imbalance of Th1/Th2.It suggested that the imbalance of local immunity is the key link of HR-HPV persistent infection and cervical cancer degeneration.

参考文献/References:

［1］　RICHARDON L A，El-ZEIN M，RAMANAKUMAR A V，et al.HPV DNA testing with cytology triage in cervical cancer screening：Influence of revealing HPV infection status［J］.Cancer Cytopathol，2015，123(12)：745-754.
［2］　袁敏，黄焜，姚立丽，等.高危型人乳头瘤病毒对宫颈病变治疗后监测临床意义研究［J］.中华肿瘤防治杂志，2017，24(4)：268-272.
［3］　翟垚青，闫文静，乔志燕.子午流注针法联合干扰素治疗对宫颈癌合并HPV 感染患者 T 淋巴细胞亚群的影响［J］.世界中医药，2018，13（5）：1242-1245.
［4］　TRINCHIERI G.Cancer immunity：lessons from infectious diseases［J］.J Infect Dis，2015，212(Suppl)：24-29.
［5］　DELIGEOROGLOU E，GIANNOULI A，ATHANASOPOU LOS N，et al.HPV infection：immunological aspects and their utility in future therapy ［J］.Infect Dis Obstet Gynecol，2013，2013：540850.
［6］　PAHNE-ZEPPENFELD J，SCHROER N，WALCH-RUCKHEIM B，et al.Cervical cancer cell-derived interleukin-6 impairs CCR7-dependent migration of MMP-9-expressing dendritic cells［J］.Int J Cancer，2014，134(9)，2061-2073.
［7］　KOSHIOL J，LINDSAY L，PIMENTA J M，et al.Persistent human papillom avirusin fection and cervical neoplasia asystematic review and meta-analysis［J］.Am J Epidemiol，2008，168(2)：123-137.
［8］　ROSITCH A F，KOSHIOL J，HUDGENS M G，et al.Patterns of persistent genital papillomavirus infection among women world-wide：a literature review and meta-analysis［J］.Int J Cancer，2013，133(6)：1271-1285.
［9］　黄虎翔,张万明,王辉.白细胞介素-4、干扰素-γ及核因子-κB p65在解淀粉芽孢杆菌致BALB/c小鼠哮喘模型中的表达［J］.新乡医学院学报,2017,34(1):18-21.
［10］　LIAO S，ZHANG W，HU X,et al.A novel "priming-boosting" strategy for immune interventions in cervical cancer［J］.Mol Immunol，2015，64(2)：295-305.
［11］　HONG J H,KIM M K,LEE I H.Association between serum cytokine profiles and clearance or persistence of high-risk human papillomavirus infection：a prospective study［J］.Int J Gynecol Cancer，2010，20(6)：1011-1016.
［12］　RAKHRA K，BACHIREDDY P，ZABUAWALA T，et al.CD4(+) T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation［J］.Cancer Cell，2010，18(5)：485-498.
［13］　李风艳，于利君.高危型人乳头瘤病毒载量与宫颈癌前病变及宫颈癌的相关性分析［J］.中国妇幼保健，2017，32(16)：3735-3737.
［14］　杨亮亮，朱义保.高危型人乳头瘤病毒负荷量与宫颈病变的关系研究［J］.实用妇产科杂志，2015，31(4)：282-284.
［15］　EGAWA N，EGAWA K，GRIFFIN H，et al.Human papillomaviruses:epithelial Tropisms，and the development of neoplasia［J］.Viruses，2015，7(7)：3863-3890.
［16］　KANTERMAN J,SADE-FELDMAN M,BANIYASH M.New insights into chronic inflammation-induced immunosuppression［J］.Semin Cancer Biol，2012，22(4)：307-318.

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更新日期/Last Update: 2019-11-05