新型免疫抑制剂FTY720通过阻断S1P信号通路诱导母胎免疫耐受的实验研究

发布时间：2018-12-17 18:28

【摘要】：目的·探讨新型免疫抑制剂FTY720诱导母胎免疫耐受的效应及机制,为临床治疗不明原因复发性自然流产提供实验依据。方法·以自然流产模型孕鼠为实验对象,观察腹腔注射FTY720对自然流产模型孕鼠胚胎丢失率及蜕膜组织1-磷酸鞘氨醇(S1P)表达的影响。构建S1P基因siRNA慢病毒载体及过表达S1P基因慢病毒载体,并转染小鼠骨髓来源树突状细胞(DCs);观察过继转移2种慢病毒载体后FTY720对自然流产模型孕鼠胚胎丢失率的影响。结果·FTY720对正常妊娠模型孕鼠的胚胎丢失率无明显影响,腹腔注射FTY720能明显降低自然流产模型孕鼠的胚胎丢失率。自然流产模型孕鼠局部蜕膜组织存在S1P的低表达。过继转移S1PsiRNA慢病毒转染的DCs后,FTY720在一定程度上能降低自然流产模型孕鼠的胚胎丢失率,但效果不及过继转移S1P-siRNA慢病毒转染的DCs前;过继转移过表达S1P基因慢病毒转染DCs后,FTY720能显著降低自然流产模型孕鼠的胚胎丢失率,其效果较过继转移过表达S1P基因慢病毒转染DCs前更为明显。结论·FTY720安全性良好,其诱导妊娠免疫耐受可能与阻断S1P信号通路有关。
[Abstract]:Objective to investigate the effect and mechanism of new immunosuppressant FTY720 on maternal and fetal immune tolerance, and to provide experimental evidence for clinical treatment of recurrent spontaneous abortion with unknown causes. Methods the effects of intraperitoneal injection of FTY720 on embryo loss rate and expression of sphingosine 1-phosphate (S1P) in decidua of pregnant rats with spontaneous abortion were observed. Construction of S1P gene siRNA lentivirus vector and overexpression of S1P gene lentivirus vector, and transfection of murine bone marrow-derived dendritic cells (DCs); to observe the effect of FTY720 on embryo loss rate of spontaneous abortion model pregnant rats after adoptive transfer of two lentivirus vectors. Results FTY720 had no significant effect on the embryo loss rate of normal pregnant rats. Intraperitoneal injection of FTY720 could significantly reduce the embryo loss rate of pregnant rats with spontaneous abortion. There was a low expression of S1P in decidual tissue of pregnant rats with spontaneous abortion. After DCs was transfected with S1PsiRNA lentivirus, FTY720 could reduce embryo loss rate of pregnant rats with spontaneous abortion to some extent, but the effect was not as good as that before DCs transfer by S1P-siRNA lentivirus transfection. FTY720 could significantly reduce the embryo loss rate of pregnant rats with spontaneous abortion after adoptive transfer of lentivirus expressing S1P gene into DCs, and the effect was more obvious than that before DCs transfection with lentivirus expressing S1P gene. Conclusion FTY720 is safe, and it may be related to blocking S 1P signaling pathway.
【作者单位】：上海交通大学附属第六人民医院妇产科;上海交通大学医学院附属国际和平妇幼保健院妇产科;
【基金】：国家自然科学基金(81200477)~~
【分类号】：R714.21

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