关键词: 流产, 习惯性；心磷脂质类；抗心磷脂抗体；膜联蛋白A2；Toll样受体4

Abstract: Background　Recurrent spontaneous abortion（RSA） is one of the common diseases in pregnancy，and anti-cardiolipin antibodies（ACA） are closely related to the occurrence of the disease.Previous studies have found that the Toll-like receptor 4 （TLR4） /NF-κB pathway in the decidua of ACA（+） RSA is activated，suggesting that the changes in factors in this pathway and pathway may be important mechanisms for the occurrence of ACA（+）RSA，so the pathway and interventions with related factors may have an impact on the pregnancy outcome of ACA（+）RSA.Because ACA（+）RSA has a tendency to thrombosis，which is consistent with the syndrome of kidney deficiency and blood stasis in Chinese medicine，so use the method of reinforcing kidney and activating blood，Kidney-nourishment & Blood-activation Recipe prepared according to the treatment method have also been obtained good effect in long-term and large-scale clinical application.Objective　To observe the effect of Kidney-nourishment and Blood-activation Recipe on peripheral blood and decidual Annexin A2 （ANXA2），TLR4 in patients with RSA and positive ACA，and then to explain the efficacy and action mechanism of Kidney-nourishment and Blood-activation Recipe in fetus protection for ACA （+） RSA patients.Methods　Thirty-one patients admitted to the outpatient and inpatient departments of First Affiliated Hospital， Heilongjiang University of Chinese Medicine from March 2015 to March 2016 were selected.Among them 16 cases had pregnancy failures and needed complete curettage of uterine cavity，and 15 patients performed normal abortion at the outpatient department.A total of 31 decidua were collected and patients were divided into test group 1 （n=16） and control group 1 （n=15）．One case was excluded from the test group 1 because of chromosome abnormality in the abortion tissue.Eleven patients were selected as test group 2 with ACA（+）RSA who asked for a fetus protection andadmitted to the outpatient and inpatient departments of First Affiliated Hospital  to Heilongjiang University of Chinese Medicine from March 2015 to March 2016，and 13 patients who received a normal pregnancy test at the outpatient department were selected as control group 2.A total of 24 serum samples were collected.Four cases were excluded from the study，as one case in the test group 2 had spontaneous abortion，and 3 cases in the control group 2 quitted the study.The levels of ANXA2 mRNA and TLR4 mRNA in decidua of patients in the control group 1 and test group 1 were detected with RT-qPCR method.The test group 2 was given Kidney-nourishment and Blood-activation Recipe，and the control group 2 was not given intervention.Their venous blood was taken before and after treatment.The levels of serum progesterone，β-HCG，ANXA2，and TLR4 of control group 2 and test group 2 were detected using the ELISA method.Results　The level of ANXA2 mRNA in the abortion decidual tissue of the control group 1 was higher than that of the test group 1 and its TLR4 mRNA level was lower than that of the test group 1 （P<0.05）．There were significant differences in levels of serum progesterone，β-HCG，ANXA2 and TLR4 between the control group 2 and the test group 2 before the treatment （P<0.05）．After the treatment，the differences in serum progesterone，β-HCG、ANXA2 and TLR4 between the control group 2 and the test group 2 was not statistically significant （P>0.05）．The levels of serum progesterone，β-HCG，ANXA2 of the test group 2 were all significantly higher than those before treatment ，level of serum TLR4 of the test group 2 was significantly lower than that before treatment（P<0.05）．Conclusion　The occurrence of ACA（+）RSA may be associated with low expression of ANXA2 and high expression of TLR4.Kidney-nourishment and Blood-activation Recipe can improve hypercoagulability and inflammation and in turn improve the pregnancy outcome by up-regulating ANXA2 and down-regulating TLR4.

Key words: Abortion, habitual；Cardiolipins；Anticardiolipin antibody；Annexin A2；Toll-like receptor 4