过继转移FTY720-DC对自然流产模型孕鼠胚胎丢失率的影响

Influence of adoptive transfer of FTY720-DC on the embryo loss rate in mice of spontaneous abortion model

目的观察过继转移FTY720-树突状细胞（FTY720-DC）对自然流产模型孕鼠胚胎丢失率的影响,并初步探讨其在诱导母胎免疫耐受中的作用机制。方法建立自然流产小鼠模型（CBA/J×DBA/2）及正常妊娠小鼠模型（CBA/J×BALB/c）,分为6组：正常妊娠模型组（CBA/J×BALB/c）、未干预自然流产模型组（CBA/J×DBA/2）、注射DC培养基（DCCM）的流产模型组、过继转移DC的流产模型组、注射FTY720的流产模型组、过继转移FTY720-DC的流产模型组。于妊娠第12~14日观察孕鼠胚胎丢失情况,同时采用流式细胞仪检测各组孕鼠外周血Treg、Th17细胞占单个核细胞的比例。结果过继转移FTY720-DC后孕鼠胚胎丢失率明显低于未干预或注射DCCM的流产模型组（P=0.00）,与过继转移DC的流产模型组和注射FTY-720的流产模型组相比,其胚胎丢失率也明显下降（P=0.01）;它与正常妊娠组胚胎丢失率的差异无统计学意义（P〉0.05）。过继转移FTY720-DC后孕鼠外周血Treg细胞比例明显增高,Th17细胞比例明显降低,与未干预或注射DCCM的流产模型组的差异有统计学意义（P=0.00）,与正常妊娠组的差异无统计学意义（P〉0.05）。结论过继转移FTY720-DC能诱导妊娠免疫耐受,降低自然流产模型孕鼠的胚胎丢失率,其机制可能是通过逆转了自然流产模型孕鼠Treg/Th17的失平衡状态。

Objective To observe the effect of adoptive transferring FTY720-dendritic cells（FTY720-DCs） on the embryo loss rate in the mouse model of spontaneous abortion and explore the mechanism of inducing maternal-fetal immune tolerance.Methods The mouse models of spontaneous abortion（CBA/J×DBA/2）and normal pregnancy（CBA/J×BALB/c） were constructed.Mice were assigned to six groups,i.e.normal pregnancy group（CBA/J×BALB/c）,spontaneous abortion with no intervention group（CBA/J×DBA/2）,abortion with DC cells culture medium（DCCM） injection group,abortion with adoptive transferring DC group,abortion with FTY720 injection group,and abortion with adoptive transferring FTY720-DC group.The embryo loss on 12th- 14 th day of gestation was observed.The proportions of Treg and Thl7 cells in peripheral blood mononuclear cells were measured with flow cytometer.Results The embryo lost rate in mice with adoptive transferring FT Y720-DC was significantly lower as compared with mice in the spontaneous abortion with no intervention group and the abortion with DCCM injection group（P=0.00）,as well as the abortion with adoptive transferring DC group and the abortion with FTY720 injection group（P=0.01）.There was no significant difference in the embryo lost rate between the abortion with adoptive transferring FTY720-DC group and the normal pregnancy group（P〉0.05）.The proportion of peripheral blood Treg cells was remarkably increased and the proportion of Thl7 cells was significantly decreased after adoptive transferring FT Y720-DC.The differences were statistically significant as compared with the spontaneous abortion with no intervention group and the abortion with DCCM injection group（P=0.00） and the difference was not statistically significant as compared with the normal pregnancy group（P〉0.05）.Conclusion Adoptive transfer of FTY720-DC can induce immune tolerance in pregnancy and decrease the embryo loss rate in mice of spontaneous abortion model.The mechanism may be associated with the reverse of the imbalance of Treg/Thl7 in mice of spontaneous abortion model.