上海交通大学学报（医学版）

›› 2011, Vol. 31 ›› Issue (7): 895-.doi: 10.3969/j.issn.1674-8115.2011.07.006

• 论著（基础研究） • 上一篇    下一篇

COX-2及其信号转导通路的表达与自身免疫型复发性流产的关系

肖世金1, 赵爱民1, 鲍世民2   

  1. 1.上海交通大学 医学院附属仁济医院妇产科, 上海 200127； 2.中国科学院 上海实验动物中心, 上海 201615
  • 出版日期:2011-07-28 发布日期:2011-07-27
  • 通讯作者: 赵爱民, 电子信箱: zam0526@yahoo.com.cn。
  • 作者简介:肖世金（1983—）, 男, 住院医师, 硕士；电子信箱: shjxiao@sina.com。
  • 基金资助:

    上海市创新行动计划基金（08140901500）

Relationship between expression of COX-2, its signal transduction pathways and autoimmune-type recurrent miscarriage

XIAO Shi-jin1, ZHAO Ai-min1, BAO Shi-min2   

  1. 1.Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200217, China；2.Experimental Animal Center of Shanghai, the Chinese Academy of Sciences, Shanghai 201615, China
  • Online:2011-07-28 Published:2011-07-27
  • Supported by:

    Shanghai Innovation Action Plan, 08140901500

PDF (PC)

1623

摘要：

目的 探讨环氧化酶2（COX-2）及其信号转导通路相关分子在自身免疫型复发性流产(RSA)发病机制中的作用。方法 83只BALB/c近交系小鼠分为实验组、子宫腔注射对照组和正常妊娠对照组。实验组包括子宫腔人β2糖蛋白1(β2GP1)注射组(n=15)、腹腔β2GP1注射组(n=10)和皮下β2GP1注射组(n=14)；子宫腔注射对照组包括子宫腔生理盐水（NS）注射组(n=10)、子宫腔无关蛋白注射组(n=6)和子宫腔佐剂注射组(n=13)；正常妊娠对照组（n=15)为未行任何干预的雌雄BALB/c合笼小鼠。比较各组小鼠的胚胎丢失率、流产率和胎盘平均质量。采用RT-PCR技术检测各组小鼠胎盘组织中COX-2及其信号转导通路相关分子前列腺素D2（PGD2）、干扰素诱导蛋白(IP)、过氧化物酶体增殖物激活型受体α（PPARα）和PPARγ的mRNA表达。结果 实验组各亚组小鼠胚胎丢失率均显著高于正常妊娠对照组(P<0.001)，胎盘平均质量均显著低于正常妊娠对照组(P<0.05)。子宫腔β2GP1注射组小鼠流产率显著高于其余各组（P<0.05）。胎盘组织中COX-2、PGD2、IP、PPARα、PPARγ mRNA表达检测结果显示：实验组各亚组均显著低于正常妊娠对照组 (P<0.05)，其中子宫腔β2GP1注射组明显低于子宫腔注射对照组(P<0.05)。结论 子宫腔注射人β2GP1可诱导建立符合自身免疫型RSA临床特征的小鼠模型，COX-2及其信号转导通路相关分子可能在自身免疫型RSA的发病中发挥重要作用。

关键词: 复发性流产, 自身免疫, 动物模型, β2糖蛋白1, 环氧化酶2

Abstract:

Objective To investigate the roles of cyclooxygenase-2 (COX-2) and its signal transduction pathway related molecules in the pathogenesis of autoimmune-type recurrent spontaneous abortion (RSA). Methods Eighty-three BALB/c mice were divided into experiment group, uterine cavity injection control group and normal pregnancy control group. Experiment group was subdivided into uterine cavity human β2 glycoprotein-1 (β2GP1) injection group (n=15), abdominal cavity β2GP1 injection group (n=10) and subcutaneous β2GP1 injection group (n=14). Uterine cavity injection control group was subdivided into uterine cavity normal saline (NS) injection group (n=10), uterine cavity unrelated protein injection group (n=6) and uterine cavity adjuvant injection group (n=13). Mice in normal pregnancy control group (n=15) did not receive any intervention. The embryo loss rates, the abortion rates and the average weight of placenta were compared among groups. The expression of COX-2 in placenta and its signal transduction pathway related molecules prostaglandin D2 （PGD2）, interferon-inducible protein (IP), peroxisome proliferators activator receptors alpha (PPARα) and PPARγ mRNA was detected by RT-PCR. Results The embryo loss rates in subgroups of experiment group were significantly higher than that in normal pregnancy control group (P<0.001), and the average weight of placenta in subgroups of experiment group was significantly lower than that in normal pregnancy control group (P<0.05). The abortion rate in uterine cavity β2GP1 injection group was significantly higher than those in the other groups （P<0.05）. The expression of COX-2, PGD2, IP, PPARα and PPARγ mRNA in placenta in subgroups of experiment group was significantly lower than that in normal pregnancy control group (P<0.05), and the expression of COX-2, PGD2, IP, PPARα and PPARγ mRNA in placenta in uterine cavity β2GP1 injection group was significantly lower than that in uterine cavity injection control group （P<0.05）. Conclusion Uterine cavity injection of human β2GP-1 can successfully establish mouse model which is consistent with the features of autoimmune-type RSA, and COX-2 and its signal transduction pathway related molecules may play important roles in the pathogenesis of autoimmune-type RSA.

Key words: recurrent miscarriage, autoimmune, animal model, β2 glycoprotein-1, cyclooxygenase-2