
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
网络出版日期: 2011-07-27
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
Online published: 2011-07-27
Supported by
Shanghai Innovation Action Plan, 08140901500
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。
肖世金, 赵爱民, 鲍世民 . 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[J]. 上海交通大学学报(医学版), 2011 , 31(7) : 895 . DOI: 10.3969/j.issn.1674-8115.2011.07.006
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
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