阿奇霉素治疗沙眼衣原体感染孕鼠对其妊娠结局及免疫状态的影响

Affection of the pregnancy outcome and immune status with azithromycin treatment on vaginal infection by chlamydial trachomatis

目的:了解沙眼衣原体感染孕鼠的妊娠结局与体内Th1型、Th2型细胞因子水平的关系,以及阿奇霉素干预治疗对其免疫状态及妊娠结局的影响,探讨沙眼衣原体致不良妊娠结局的免疫机理。方法:随机将孕鼠分成3组,于孕2、3、4天,对照组阴道内接种无感染衣原体由McCoy细胞制备的SPG悬液30μl,模型组阴道内接种1.0×106IFU/ml沙眼衣原体F型株的SPG悬液30μl,给药组阴道接种衣原体后于妊娠第8天腹腔注射阿齐霉素10mg/kg(单次给药)。孕12天用酶联免疫法检测各组小鼠血清中Th1型(IFN-γ、TNF-α)/Th2型(IL-4、IL-10)细胞因子表达水平,计算IL-4/TNF-α,IL-10/TNF-α比率。用方差分析和χ2检验比较3组的妊娠失败率、胚胎吸收率、胎重、孕期体重增加量等,以及3组之间细胞因子水平及Th1/Th2型免疫调节平衡的比率等。结果:模型组与对照组比较体内Th2型细胞因子下降(IL-10),而Th1型细胞因子上升(TNF-α),且代表Th1/Th2型免疫调节平衡的细胞因子比值:IL-4/TNF-α,IL-10/TNF-α模型组显著低于对照组,形成Th1型免疫偏倚。给药组降低了妊娠失败率并降低了Th1型免疫偏倚程度。模型组小鼠妊娠失败率及反复妊娠失败率显著高于对照组;给药组小鼠妊娠失败率较模型组低而较对照组高,反复妊娠失败率较模型组下降明显(P<0.05);3组的胚胎吸收率,胚重,孕期体重增加量无显著差异。结论:阴道接种沙眼衣原体使体内细胞因子向Th1型漂移,增加了小鼠的妊娠失败率;阿奇霉素干预可降低Th1型漂移程度,降低小鼠妊娠失败率。

Objective：To explore chlamydial trachomatis（CT） infection transvaginally in a murine model and to observe pregnancy-related outcomes as a result of CT inoculation and azithromycin treatment,and to investigate the levels of Th1 type and Th2 type cytokine.Methods：All pregnant mice were randomly divided into three groups.On days 2,3,and 4 of gestation,the control group was inoculated intravaginally with 30μl of SPG without CT,while the model group was inoculated with 106 IFU/ml CT in 30μl of SPG,and the administration group was injected azithromycin 10mg/kg（single administration） intraperitoneally on day 8 of gestation.On day 12 of gestation,the mice were sacrificed,and differences between groups in conception rate,embryo resorption rate,embryo weight,and maternal weight increment and the serum cytokine levels of Th1（IFN-γ、TNF-α）/Th2（IL-4、IL-10） were compared by the unpaired Student＇s t test and by the χ2 test.Results：Th2-type cytokines（IL-10） of the model group was decreased and Th1-typ cytokines（TNF-α） was increased.Azithromycin treatment group reduced the failure rate of pregnancy and the level of Th1-type immune bias;the percentage of mice that achieved successful conception was significantly higher than the model group;there were no differences between groups in embryo resorption rate,embryo weight,or maternal weight increment.Conclusion：CT infection of the lower genital tract is associated with Th1-type immune bias and conception but not with embryo resorption rate,embryo weight,or maternal weight increment.