环孢素A对反复自然流产小鼠妊娠的影响

Effect of cyclosporine A on pregnancy outcome in mice with recurrent spontaneous abortion

目的探讨环孢素A对反复自然流产小鼠妊娠的影响及机制。方法雌性CBA/J小鼠与雄性DBA/2小鼠合笼交配构建反复自然流产小鼠模型,并随机分为模型组和低、中、高剂量实验组,每组10只;同时选取10只正常妊娠小鼠为对照组;于妊娠第4天,低、中、高剂量实验组分别予以腹腔注射5,10,20mg·kg^-1环孢素A,模型组和对照组注射等量0.9%Na Cl。用酶联免疫吸附(ELISA)法检测各组小鼠血清中γ-干扰素(IFN-γ)、白细胞介素10(IL-10)含量,用Western blot检测各组小鼠蜕膜和胎盘组织IL-8蛋白表达,统计各组小鼠胚胎吸收率。结果对照组、模型组和低、中、高剂量实验组血清IFN-γ分别为(36.59±5.02),(85.46±7.09),(54.11±8.59),(53.05±10.26),(54.18±8.46)pg·m L^-1;血清IL-10分别为(1056.28±235.16),(698.45±156.24),(1136.52±169.42),(1152.46±174.25),(1149.68±139.51)pg·L^-1;IL-8蛋白相对表达量分别为0.43±0.04,1.36±0.24,0.56±0.05,0.52±0.11,0.55±0.13;胚胎吸收率分别为(4.56±0.16)%,(23.85±0.25)%,(4.36±0.13)%,(6.26±0.35)%,(12.36±0.22)%。低、中、高剂量实验组的上述指标分别与模型组比较,差异均有统计学意义(均P<0.05)。结论环孢素A可改善反复自然流产小鼠妊娠结局,与调控Th1细胞向Th2方向分化,下调母胎界面IL-8蛋白表达有关。

Objective To investigate the effect and mechanism of cyclosporine A on pregnancy outcome in mice with recurrent spontaneous abortion.Methods A model of recurrent spontaneous abortion was established by mating female CBA/J mice in cage with male DBA/2 mice,and then the successfully modeled mice were randomly assigned to model group and experimental-L/-M/-H groups with 10 mice in each group.At the same time,10 normal pregnant mice were selected as control group.On the fourth day of pregnancy,experimental-L/-M/-H groups were injected with cyclosporine A 5,10,20 mg·kg^-1 intraperitoneally,and 0.9%NaCl was injected into model group and control group.The serum levels of interferon-γ(IFN-γ)and interleukin-10(IL-10)were detected by enzyme-linked immunosorbent assay(ELISA).The expression of IL-8 in decidua and placenta tissues was detected by Western blot,and the embryo absorption rate was counted.Results The levels of IFN-γin serum were(36.59±5.02),(85.46±7.09),(54.11±8.59),(53.05±10.26),(54.18±8.46)pg·m L^-1,IL-10 were(1056.28±235.16),(698.45±156.24),(1136.52±169.42),(1152.46±174.25),(1149.68±139.51)pg·L^-1,the relative expression of IL-8 protein were 0.43±0.04,1.36±0.24,0.56±0.05,0.52±0.11,0.55±0.13,respectively,the embryo absorptivity were(4.56±0.16)%,(23.85±0.25)%,(4.36±0.13)%,(6.26±0.35)%,(12.36±0.22)%,respectively.There were statistically significant differences between the model group and the experimental-L/-M/-H groups in the above indices(P<0.05).Conclusion Cyclosporin A can improve the pregnancy outcome of mice with recurrent spontaneous abortion,which is related to regulate the differentiation of Th1 cells into Th2 cells and down-regulate the expression of IL-8 protein at the maternal-fetal interface.