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

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...

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Published in上海交通大学学报（医学版） Vol. 37; no. 10; pp. 1332 - 1336
Main Author 熊苗 徐亮 李莉 刘阳 周芳芳 王军 朱洁萍
Format Journal Article
LanguageChinese
Published 上海交通大学附属第六人民医院妇产科,上海,200233%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 2017
Subjects
1-磷酸鞘氨醇信号通路
FTY720
妊娠免疫耐受
母胎界面
pregnancy immune tolerance
母胎界面
maternal-fetal interface
FTY720
sphingosine-1-phosphate signaling pathway
1-磷酸鞘氨醇信号通路
妊娠免疫耐受
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Summary: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。
Bibliography: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 mi
ISSN:1674-8115
DOI:10.3969/j.issn.1674-8115.2017.10.004