Regulating Effects of Kidney-nourishment & Blood-activation Decoction on COX-2，PGE2 in Serum and Decidua of ACA（+） RSA Patients

doi:10.12114/j.issn.1007-9572.2020.00.185

Abstract

Abstract: Background　Recurrent spontaneous abortion（RSA） is one of the common diseases during pregnancy.Current etiological research shows that ACA（+） is closely related to its pathogenesis.COX-2 plays a role in regulating platelet aggregation and peripheral vasoconstriction，and catalyzing the inducible production of prostaglandin.So COX-2 and COX-2-catalyzed synthesis of PGE2 may be associated with ACA（+） RSA with the trend of blood hypercoagulability and affect pregnancy outcomes.Objective　Clarify the relationship between ACA（+） RSA and the abnormal expression of its COX-2 and PGE2, and explore the therapautical effect and molecular mechanism of method of invigorating the Kidney-nourishment & blood-activation decoction（KBD） to ACA（+） RSA.Methods　All the participants were recruited from First Affiliated Hospital，Heilongjiang University of Chinese Medicine during March 2015 to March 2016，including 16 ACA（+） outpatients and inpatients with a history of RSA and current pregnancy loss undergoing curettage（experimental group 1），11 ACA（+） RSA outpatients and inpatients with a history of RSA undergoing tocolytic therapy due to possible miscarriage symptoms and signs during current pregnancy（experimental group 2），15 outpatients undergoing normal artificial abortion（control group 1），and 13 cases undergoing normal antenatal care（control group 2）.RT-PCR was used to detect the expression levels of COX-2 and PGE2 mRNA in decidua samples of experimental group 1 and control group 1，but 30 cases were finally included（one case in the experimental group 1 was excluded later because chromosome abnormality was found to be the culprit for RSA）.The experimental group 2 received KBD，while control group 2 received no interventions.ELISA was used to measure the expression levels of COX-2 and PGE2 in venous blood samples of experimental group 2 and control group 2 before and after the intervention period.Finally，only 20 cases in these two groups were enrolled because one case in the experimental group 2 was excluded due to later spontaneous abortion，and three cases in control group 2 actively dropped out.Results　（1）The control group 1 showed higher mean expression levels of COX-2 mRNA and PGE2 mRNA in decidual tissues compared with experimental group 1（P<0.05）.（2）At baseline，the control group 2 and experimental group 2 had significant differences in mean serum progesterone，β-HCG，COX-2 and PGE2 levels（P<0.05）.But after receiving KBD，the experimental group 2 showed insignificant different mean levels of serum progesterone，β-HCG，and COX-2（P>0.05），and higher mean serum level of PGE2 compared with the control group 2（P<0.05）.（3）Serum progesterone，β-HCG，COX-2 and PGE2 increased significantly in experimental group 2 after treatment（P<0.05）.Conclusion　Decreased expression levels of COX-2 and PGE2 in serum and decidual tissues of ACA（+） RSA patients indicate that both COX-2 and PGE2 may be involved in the occurrence of the disease.And KBD contributes to the maintenance of pregnancy possibly by regulating COX-2 and PGE2.

Key words: Abortion, habitual；Anticardiolipin antibody；Cyclooxygenase 2；Dinoprostone；Kidney-nourishment &, blood-activation decoction

摘要： 背景　复发性流产（RSA）是妊娠常见疾病之一，目前的病因学研究表明，抗心磷脂抗体（ACA）（+）与其发病机制密切相关。环氧化酶2（COX-2）具有调节血小板聚集、外周血管收缩等功能，可以催化产生前列腺素E2（PGE2），COX-2及其催化产生的PGE2可能与血液高凝倾向的ACA（+）RSA存在联系，并影响其妊娠结局。目的　明确ACA（+）RSA的COX-2、PGE2异常表达与该疾病的关系，并探索补肾活血方对ACA（+）RSA疾病的治疗作用与分子机制。方法　选取2015年3月—2016年3月在黑龙江中医药大学附属第一医院门诊及住院部治疗的符合纳入标准的ACA（+）RSA流产蜕膜16例，正常流产蜕膜15例，共收集蜕膜样本31例：ACA（+）RSA者蜕膜为试验组1（n=16）、正常人工流产者蜕膜为对照组1（n=15），其中试验组1中1例因流产组织发现染色体异常而排除。选取2015年3月—2016年3月在黑龙江中医药大学附属第一医院门诊及住院部治疗的符合研究标准的要求行保胎治疗ACA（+）RSA患者11例（试验组2），及在黑龙江中医药大学附属第一医院门诊行正常孕检者13例（对照组2），共收集血清样本24例，其中试验组2中1例自然流产、对照组2中3例自动退出，未计入统计数据。采用RT-PCR法检测蜕膜组织中COX-2、PGE2的mRNA；试验组2给予补肾活血方治疗，对照组2不给予干预，于治疗前和治疗后分别留取静脉血。采用ELISA法检测血清COX-2、PGE2水平。结果　对照组1蜕膜组织中COX-2 mRNA、PGE2 mRNA水平均高于试验组1（P<0.05）。治疗前对照组2和试验组2血清P、β-HCG、COX-2、PGE2水平比较，差异有统计学意义（P<0.05）；治疗后对照组2和试验组2血清P、β-HCG、COX-2水平比较，差异无统计学意义（P>0.05）；治疗后对照组2血清PGE2水平低于试验组2（P<0.05）。试验组2治疗后血清P、β-HCG、COX-2、PGE2 水平均高于治疗前（P<0.05）。结论　ACA（+）RSA患者血清、蜕膜组织中COX-2、PGE2呈低表达，提示COX-2、PGE2可能参与该病的发生。补肾活血方可以通过调节COX-2、PGE2水平而有利于ACA（+）RSA者维持妊娠。

关键词: 流产, 习惯性；抗心磷脂抗体；环氧化酶2；地诺前列酮；补肾活血方

CHANG Zhuo,LI Na,ZHANG Yang, et al. Regulating Effects of Kidney-nourishment & Blood-activation Decoction on COX-2，PGE2 in Serum and Decidua of ACA（+） RSA Patients　[J]. Chinese General Practice, 2020, 23(9): 1158-1163. DOI: 10.12114/j.issn.1007-9572.2020.00.185.
常卓,李娜,张杨等. 补肾活血方对抗心磷脂抗体阳性复发性流产患者血清和蜕膜中环氧化酶2及前列腺素E2的影响研究[J]. 中国全科医学, 2020, 23(9): 1158-1163. DOI: 10.12114/j.issn.1007-9572.2020.00.185.

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