HPV16型存在状态与Treg／Th17细胞因子的相关性研究  

Correlation study of HPV-16 existential status with Th17/Treg cytokines

作　　者：丁爱萍 张瑶[1] 魏恒[1] 罗清双[1] 张淑兰[1] 

机构地区：[1]中国医科大学附属盛京医院妇产科,沈阳110004 [2]江苏省常州市妇幼保健院妇产科,213000

出　　处：《中华医学杂志》2013年第37期2957-2960,共4页National Medical Journal of China

基　　金：国家自然科学基金（81372776）;辽宁省医学高峰建设工程项目（2010696）;辽宁省科学技术计划项目（2011225009）;盛京自由研究者计划（200806）;沈阳市科学技术计划项目（F11-262-9-15）

摘　　要：目的 探讨人乳头状瘤病毒（HPV） 16 DNA存在状态与调节性T细胞（Treg）表面标志物Foxp3＋的表达及外周血Treg/Th17相关细胞因子的关系和在宫颈癌进展中的作用和意义.方法 收集2012年1至10月于中国医科大学附属盛京医院妇科142例HPV16＋病例,分为宫颈鳞癌（CC,60例）,宫颈上皮内瘤变（CIN,65例）,对照组（健康妇女,17例）.采用多重实时PCR技术检测宫颈脱落细胞的E2和E6基因,通过E2/E6比值法评估HPV16型DNA的体内存在状态.采用免疫组化方法检测宫颈组织中Foxp3＋调节性T细胞表达.采用酶联免疫吸附试验（ELISA）方法检测Treg/Th17相关细胞因子：转化生长因子-β（TGF-β）、白细胞介素（IL）-10、17、21.结果 （1）在HPV16DNA体内同一种存在状态下,CIN和CC组Foxp3＋比例及TGF-β、IL-10浓度较对照组明显升高（P＜0.01）;IL-17、IL-21浓度较对照组明显降低（P＜0.05）;（2）在同一病变条件下,HPV16 DNA整合率随着Foxp3＋、TGF-β、IL-10表达增加而升高,随着IL-21、IL-17表达降低而升高;（3）不同HPV16型DNA存在状态的宫颈癌中Foxp3＋表达与FIGO分期、组织学分级及淋巴结转移密切相关（P＜0.05）,而与年龄无关（P＞0.05）.结论 Treg细胞因子与HPV16整合率和宫颈病变严重程度呈正相关,而Th17细胞因子与其呈负相关.Treg/Th17细胞因子在HPV持续感染所致宫颈癌的发生发展中可能起着重要作用.Objective To explore the relationship between the presence of HPV-16 DNA and the expression Treg surface marker Foxp3 ＋,peripheral blood levels of Th17/Treg cell-associated cytokines and explore their roles and significance in cervical cancer progression.Methods Between January 2012 and October 2012 at Shengjing Hospital of China Medical University,a total of 142 HPV16 positive patients were divided into cervical cancer （CC,n =60）,cervical intraepithelial neoplasia （CIN,n =65） and control group （n =17）.Cervical liquid-based cytological （LBC） samples were collected to detect E2 and E6 genes of HPV type 16 using multiple real-time polymerase chain reaction （PCR）.E2/E6 ratio was used to evaluate the physical status of HPV-16 DNA in host cell genome.The SP immunohistochemical method was used to detect the expressions of FOXP3 in cervical lesions.The concentrations of Th17/Treg cell-associated cytokines were detected by enzyme-linked immunosorbent assay （ELISA）.Results Under the same status of HPV16 DNA in vivo,the levels of Foxp3 ＋,transforming growth factor-β （TGF-β） and interleukin-10 （IL-10） were significantly higher than those of the control group（P 〈 0.01） while the levels of interleukin-17 （IL-17） and interleukin-21 （IL-21） were significantly lower than those of the control group （P 〈 0.05）.In the same disease,HPV16 DNA integration rate grew with the increases of Foxp3 ＋,TGF-β and IL-10 while IL-17 and IL-21 were opposite.In the different status of HPV16 type DNA,the expression of Foxp3 ＋ was closely correlated with Federation International of Gynecology and Obstetrics （FIGO） stage,histological grade and lymphnode metastasis （P 〈 0.05） except for age （P 〉 0.05）.Conclusion Treg cytokines,HPV16 integration rate and severity of cervical lesions are positively correlated while Th17 cytokines show opposite effects.Th17/Treg cell-associated cytokines may play an important role in the occurrence and development of cervical cancer.

关 键 词：宫颈肿瘤 T淋巴细胞 调节性 人乳头状瘤病毒16 病毒整合 

分 类 号：R737.33[医药卫生—肿瘤]