抗心磷脂抗体阳性复发性流产小鼠胎盘的差异蛋白组学研究

目的 探讨抗心磷脂抗体(ACA)阳性复发性流产小鼠胎盘组织中蛋白的表达谱特征并进行生物信息学分析.方法 将20只雌性BALB/c小鼠随机分为正常对照组和ACA阳性流产模型组,每组10只.模型组于第1天和第8天通过腹腔注射β2-糖蛋白Ⅰ(β2-GPI)建立ACA阳性流产模型,正常对照组于相同时间注射等体积生理盐水,腹腔注...

Differential proteomics study on placenta of mice with anticardiolipin antibody positive recurrent abortion

Objective:To analyze the protein expression profiles and bioinformatics in the placenta of mice with anticardiolipin antibody(ACA)positive recurrent abortion.Methods:Twenty female BALB/c mice were randomly divided into normal control group and ACA positive abortion model group with 10 mice in each group.The mouse model of ACA positive abortion was established by injecting intraperitoneally with 2-glycoprotein I(β2-GPI)on the first and eighth days,and the normal group was injected with equal volume of normal saline at the same time.On the 18th day after intraperitoneal injection,the male and female cages were 1∶1,and the pregnancy time was observed and recorded.On the 15th day of pregnancy,the mice were killed,the weight of fetus and placenta were measured,and the embryo loss rate was calculated.The ACA level in placenta was detected by ELISA.The differentially expressed proteins(DEPs)in the placentas of mice in each group were screened by using Label-free proteomics and Go enrichment,KEGG pathway and protein interaction network analysis were performed.Hypoxia inducible factor-1α(HIF-1α),toll like receptor 4(TLR-4),thrombin sensitive protein-1(TSP-1),T cell immunoglobulin mucin molecule-3(Tim-3)and retinoic acid related orphan receptor gamma t(RORγt)were selected for Western blot validation.Results:Compared with normal control mice,the weights of fetus and placenta were decreased,the embryo loss rate was increased and the ACA level in serum and placenta were increased.Compared with normal control mice,87 DEPs were identified in ACA positive mouse placenta,35 of which were significantly up-regulated and 52 significantly down-regulated.Go analysis showed that the DEPs were mainly located extracellular region and involved in the regulation of transmembrane transport activity.KEGG analysis showed that the DEPs were mainly concentrated in metabolism and phospholipase D signaling pathways.Interaction analysis showed that 39 DEPs interacted with each other.The results of Western blot were consistent with those of proteomics.Conclusions:The mouse model of ACA positive abortion was established successfully.The protein expression profiles in the placenta of ACA positive abortion mice were significantly changed.The differential expression proteins are related with transmembrane transport and metabolic pathway.Therefore,it is speculated that the differential expression of these proteins may be the causes of ACA positive abortion.