调节性T细胞对LPS诱导的小鼠早产模型胎盘炎症反应的影响

Effect of regulatory T cells on placental inflammation in lipopolysaccharide-induced preterm delivery mouse models

目的研究调节性T细胞对脂多糖(LPS)诱导的小鼠早产模型胎盘炎症反应的影响。方法孕17 d小鼠分组为腹腔注射PBS组(Control组),腹腔注射LPS(LPS组),腹腔注射LPS并尾静脉注射PBS组(LPS+PBS组),腹腔注射LPS并尾静脉注射Treg组(LPS+Treg组)。构建LPS腹腔注射诱导的17 d孕小鼠早产模型。在第2剂LPS注射后1、6、12 h及出生时留取胎盘组织,检测Treg细胞标志物叉头翼状螺旋转录因子(Foxp3)、白血病抑制因子(LIF)、血红素加氧酶-1(HO-1)和白介素6(IL-6)mRNA及蛋白表达水平。结果 1 LPS组早产率100%,Control组未发生早产,LPS+Treg组早产率与LPS组和LPS+PBS组差异无统计学意义(P>0.05)。2 LPS组与LPS+PBS组胎盘组织中Foxp3、HO-1、LIF在第二剂LPS注射后1、6、12 h及出生时表达显著下降,IL-6表达显著增高;LPS+Treg组Foxp3、HO-1、LIF表达明显增高,IL-6表达显著降低。结论在LPS腹腔注射诱导的早产小鼠模型中,胎盘组织Treg减少可能是早产的机制之一,HO-1、LIF参与了Treg在母胎界面维持的独特的免疫微环境;Treg过继治疗可通过降低IL-6的表达减轻胎盘组织炎症反应。

Objective To explore the effect of the regulatory T cells on placental inflammation in lipopolysaccharide（ LPS）-induced preterm delivery mouse models. Methods The 17-day-old pregnant mice were divided into phosphate buffer saline（ PBS） group（ control group） with intraperitoneal injection of PBS,LPS group with intraperitoneal injection of LPS,LPS ＋ PBS group with intraperitoneal injection of LPS and tail vein injection of PBS,and LPS ＋ Treg group with intraperitoneal injection of LPS and tail vein injection of PBS. LPS-induced preterm delivery models of 17-day-old pregnant mice were established. Placenta tissues were taken for detecting the expression levels of forkhead / winged helix transcription factor（ Foxp3）,leukemia inhibitory factor（ LIF）,heme oxygenase-1（ HO-1） and interleukin 6（ IL-6） 1,6,12 h after the second injection of LPS and at birth. Results Premature delivery rate was 100% in LPS group and 0% in control group. There was no significant difference between LPS ＋ Treg group and LPS ＋ PBS group（ P〈0. 05）. The expression levels of Foxp3,HO-1,and LIF decreased significantly,while the level of IL-6 increased significantly in LPS group and LPS ＋ PBS group. The expression levels of Foxp3,HO-1,LIF increased significantly in LPS ＋ Treg group,and the expression level of IL-6 decreased significantly 1,6,12 h after the second injection of LPS and at birth. Conclusion In LPS-induced preterm delivery mouse models,decreasing of the placenta tissue Tregs might be one of mechanisms of premature delivery,HO-1 and LIF participate in the unique immune microenviroment kept by Tregs in maternal-fetal interface. Tregs adoptive therapy can relieve the inflammation reaction of placenta tissue by lowering the expression level of IL-6.