上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2017, Vol. 37 ›› Issue (10): 1332-.doi: 10.3969/j.issn.1674-8115.2017.10.004

• 论著（基础研究） • 上一篇    下一篇

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

熊苗 1，徐亮 2，李莉 1，刘阳 1，周芳芳 1，王军 1，朱洁萍 1   

  1. 上海交通大学 附属第六人民医院妇产科，上海 200233；2. 上海交通大学 医学院附属国际和平妇幼保健院妇产科，上海 200030
  • 出版日期:2017-10-28 发布日期:2017-11-01
  • 通讯作者: ?朱洁萍，电子信箱：sweetmiaomiao@126.com
  • 作者简介:?熊苗（1981—），主治医师，硕士；电子信箱：sweetmiaomiao@126.com
  • 基金资助:
    国家自然科学基金（81200477）

Experimental research of pregnancy immune tolerance induced by a novel immunosuppressive agent FTY720 via blocking the S1P signaling pathway#br#

XIONG Miao1, XU Liang2, LI Li1, LIU Yang1, ZHOU Fang-fang1, WANG Jun1, ZHU Jie-ping1   

  1. 1. Department of Obstetrics and Gynecology, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233, China; 2. Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
  • Online:2017-10-28 Published:2017-11-01
  • Supported by:
     National Natural Science Foundation of China, 81200477

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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。

关键词: &ensp, 1- 磷酸鞘氨醇信号通路, 妊娠免疫耐受, 母胎界面, FTY720

Abstract:

Objective · To investigate the effects and mechanisms of pregnancy immune tolerance induced by a novel immunosuppressive agent FTY720 and to provide experimental basis for the clinical treatment of unexplained recurrent spontaneous abortion.  Methods · The mice of spontaneous abortion model were used as subjects. The effects of intraperitoneal injection of FTY720 on the embryo loss rate in mice of spontaneous abortion model and on the expression of sphingosine-1-phosphate (S1P) in the decidual tissue were observed. S1P-siRNA lentiviral vectors and S1P-overexpression gene lentiviral vectors were constructed and transfected into dendritic cells (DCs) from mouse bone marrow. The effects of FTY720 on the embryo loss rate in mice of spontaneous abortion model after adoptive transferring of these two types of lentiviral vectors were observed.  Results · FTY720 had no significant effect on the embryo loss rate in normal pregnant mice. Intraperitoneal injection of FTY720 significantly reduced the embryo loss rate in mice of spontaneous abortion model. The expression of S1P in the decidual tissue in mice of spontaneous abortion model was low. After adoptive transferring of S1P-siRNA lentiviral vector transfected DCs, FTY720 could slightly reduce the embryo loss rate in mice of abortion mouse model, but the effect was far less than that of before adoptive transferring of S1P-siRNA lentivirus transfected DCs. After adoptive transferring of the S1P-overexpression gene lentiviral vector transfected DCs, FTY720 could significantly reduce the rate of embryo loss in mice of spontaneous abortion model and the effect was more significant than that of before adoptive transfecting of S1P-overexpression lentiviral vector transfected DCs.  Conclusion · FTY720 is safe. The induction of pregnancy immune tolerance may be related to the blockage of S1P signaling pathway.

Key words: sphingosine-1-phosphate signaling pathway, pregnancy immune tolerance, maternal-fetal interface, FTY720