TLRs在宫颈HPV16持续性感染及宫颈病变中的作用研究

摘要

Objective:To investigate the role of TLRs in cervical HPV16 persistent infection and cervical lesions.Methods:Expressions of TLR3,TLR7,TLR8 and TLR9,which exist in cervical exfoliated cells,were detected and explored in cervical HPV16 persistent infection and cervical lesions with the method of PCR.Their expressions were compared among the HPV16 persistent infection group,HPV16 non-persistent infection group,cervical inflammation group,high-grade CIN group and cervical cancer group.Results:①Expression levels of TLR3 in HPV16 persistent infection group and HPV16 non-persistent infection group were identified to be O.622 ±0.160 and 0.696 ±0.155respectively while expression levels of IFN-β were 0.640 ±0.169 and 0.735 ±0.151,showing that both TLR3 and IFN-β demonstrated a higher level of expression in HPV16 non-persistent infection group than in HPV16 persistent infection group (t =6.574,P =0.011;t =4.378,P =0.038).LR3 DNA was positively correlated with IFN-β DNA(r=0.693,P ＜0.001),TLR9 DNA was negatively correlated with IFN-β DNA(r=-0.384,P ＜0.001).②Ranging from cervical inflammation,high-grade CIN to cervical cancer,TLR3 DNA expression levels were examined to be 0.661 ±0.159,0.606 ±0.143 and 0.507 ±0.160 respectively;IFN-β DNA expression levels were 0.722 ±0.169,0.659 ±0.144 and 0.483 ±0.143 respectively;TLR7 DNA expression levels were examined to be 0.737 ±0.198) 0.754 ±0.206 and 0.864 ±0.167 respectively;TLR9 DNA expression levels were examined to be 0.531 ±0.172,0.606 ±0.192 and 0.701 ±0.200 respectively.The expression levels of TLR3 DNA and IFN-β DNA decreased with the progression of cervical lesions(F=7.983,P ＜0.001;F=12.163,P ＜ 0.001),while the expression levels of TLR7 DNA and TLR9 DNA showed an opposite trend(F=3.647,P =0.028;F=9.415,P ＜ 0.001).Conclusions:TLRs may involve in the HPV16-removing process of the cervical local immune system.Expression level reduction of TLR3 may affect the cervical local immune function by down-regulating the expression level of IFN-β,resulting in HPV16 persistent infection.The abnormal expression of TLR3,TLR7 and TLR9 may be played an important role in the occurrence and progression of cervical lesions.%目的:探讨Toll样受体(TLRs)在宫颈人乳头瘤病毒(HPV) 16持续性感染及宫颈病变中的作用.方法:以PCR法检测宫颈脱落细胞中TLR3、TLR7、TLR8、TLR9及干扰素β(IFN-β)基因在宫颈HPV16持续性感染及宫颈病变中的表达,并分为HPV16持续感染组与HPV16非持续感染组及宫颈炎症及CIN Ⅰ组、高级别CIN和原位癌组、宫颈浸润癌组进行比较分析.结果:①在HPV16持续感染组与HPV16非持续感染组中,TLR3 DNA表达量分别为0.622±0.160、0.696±0.155,干扰素β(IFN-β) DNA表达量分别为0.640±0.169、0.735 ±0.151,TLR3、IFN-β DNA在HPV16持续感染组表达量低于HPV16非持续感染组(t=6.574,P=0.011;t =4.378,P=0.038);TLR3 DNA与IFN-βDNA呈正相关(r=0.693,P＜0.001),TLR 9DNA与IFN-βDNA呈负相关(r=-0.384,P＜0.001).②在宫颈炎症及CIN Ⅰ组、高级别CIN和原位癌组、宫颈浸润癌组中,TLR3 DNA表达量分别为0.661±0.159、0.606±0.143、0.507±0.160,IFN-β表达量分别为0.722±0.169、0.659±0.144、0.483±0.143,TLR7DNA表达量为0.737±0.198、0.754±0.206、0.864±0.167,TLR9DNA表达量为0.531±0.172、0.606±0.192、0.701±0.200.TLR3、IFN-βDNA表达量随宫颈病变进展而逐渐下降(F =7.983,P＜0.001;F=12.163,P＜0.001),而TLR7、TLR9 DNA表达量则随宫颈病变进展而逐渐增高(F =3.647,P=0.028;F =9.415,P＜0.001).结论:TLRs可能参与宫颈局部免疫系统对HPV16的清除过程,TLR3表达减低可能通过下调IFN-β表达而影响宫颈局部免疫功能,从而导致HPV16持续性感染.TLR3、TLR7、TLR9异常表达在宫颈病变发生及进展中可能发挥重要作用.