The Network Pharmacology Study And Clinical Observation Of Bushen Zhuyun Decoction In The Treatment Of Recurrent Miscarriage

Research Background:Recurrent spontaneous abortion refers to a spontaneous abortion that occurs twice or more times with a partner of the same sex,accounting for about 5%of women in the reproductive period.Modern medicine believes that due to its complicated etiology,and the cause of 50%of patients still unclear,the incidence of this disease is still high in China,causing great harm to the body and mind and family of women in the reproductive period,and actively preventing spontaneous abortion.The recurrence of the disease has important clinical and social significance for the reproductive health of women of childbearing age.Prevention and treatment of recurrent spontaneous abortion has become a hot and difficult point in the field of reproductive medicine.The disease belongs to the category of "slipper" and "several abortion" in traditional Chinese medicine.Traditional Chinese medicine has a long history of treating this disease,and it has good effects and obvious advantages.In the previous research,we put forward the importance of pre-pregnancy intervention in the treatment of recurrent abortion.Professor Cai Lianxiang,a famous doctor of the capital,created a kidney-based theory based on the theory of"treatment of disease" and "pre-cultivation of damage".The kidney-reinforcing prescription(Tusizi,Taizishen,etc.)which takes into account the spleen and stomach and pays attention to nourishment.And through the results of the previous small sample test,the pregnancy rate of pregnant women after pregnancy and pregnancy after pregnancy is significantly improved,which can effectively prevent the recurrence of spontaneous abortion.The existing problems:The mechanism and molecular aspects of the effective prescription of Bushen Zhuyun Decoction for the treatment of recurrent abortion have not been thoroughly studied.At the same time,it is necessary to further objectively observe and evaluate the curative effect of Bushen Zhuyun Recipe.At present,based on the method of network pharmacology in the era of big data,it has opened up a new path for research on the mechanism of Chinese medicine and compound action,the research and development of new drugs,and the compatibility of prescriptions.Research purposes:Based on the network pharmacology research method,we explored the effective components,targets and mechanism of the eight traditional Chinese medicines for the treatment of recurrent spontaneous abortion from the perspective of network pharmacology.At the same time,based on the previous research,the sample size was expanded to further observe the effect of the pre-pregnancy intervention on the treatment of recurrent spontaneous abortion caused by insufficient luteal function,which provided some evidence for the scientific validity of the method and laid the foundation for the development of new drugs.Research Content:Part I:Literature ReviewSummary 1:Progress in modern medical research on recurrent abortion:Through literature research,summarize the research progress of modern medicine on the etiology,pathogenesis and treatment of recurrent spontaneous abortion.Summary 2:Progress in TCM research on recurrent spontaneous abortion:Through literature research,review and summarize the status of knowledge,treatment and research on recurrent abortion in traditional Chinese medicine.Summary 3:Research progress in network pharmacology:Through literature research,summarize the concept of network pharmacology,research ideas and research progress in the field of traditional Chinese medicine.Part ?:Clinical ResearchResearch one:Network Pharmacology Study of Bushen Zhuyun Decoction in Treating Recurrent Abortion1.Research methods:Through the BATMAN database to query the composition of each Chinese medicine and possible targets,obtain the compound ingredient name and corresponding target of the 8 Chinese herbs of Bushen Zhuyun.Through the CTD database to find the target of the disease,the relevant target of the disease is predicted to be introduced into the String protein-protein interaction database,the results are exported and the target-target PPI network is constructed by Cytoscape software,and the disease is screened by the plug-in Network Analyzer.Key targets.Targeted Chinese medicine targets were docked with disease-related targets to obtain possible effective targets,and Cytoscape 3.2.1 soft-ware was used to construct an effective chemical component-disease target network map for the treatment of recurrent spontaneous abortion in Chinese medicine.Finally,the ClueGO plug-in key target of the drug was used for gene function and metabolic pathway analysis.2.Research results:(1)There are a total of 192 effective active ingredients in the Bushen Zhuyun Decoction acting on 52 targets of the disease.Screening of AKT1,TNF,TP53,VEGFA,EDN1,NOS3,CASP3,FN1,CAT,PPARG,TGFB1,HMOX1,ADIPOQ,CREB1,CTG,IL4,REN,NOS2,AGT,SLC2A4,MPO,NOS1,PRKG1,a total of 23 A key target protein for the disease.According to the results and network diagram,different effective chemical components in Bushen Zhuyun Decoction can act on the same target,and can also act on different targets,fully embodying the synergistic effect of multi-component and multi-target of Bushen Zhuyun Recipe,further proof The characteristics of "multi-component,multi-target" of traditional Chinese medicine pharmacology.(2)The biological process of regulating disease:GO enrichment analysis showed that Bushen Zhuyun Decoction may regulate the response to acidic chemicals,neuronal death,Endo+A9:A31 cell migration,response to glucocorticoids,reactive oxygen metabolism,and exogenous apoptosis.Negative regulation of signaling pathways,exogenous apoptotic signaling pathways,brown fat cell differentiation and other life activities,to achieve the role of treatment of recurrent spontaneous abortion,speculated to be able to regulate the biological process of the disease as a whole.(3)Regulate the renin signaling pathway:KEGG analysis showed that there were 15 channels for Bushen Zhuyun Decoction in the treatment of recurrent spontaneous abortion.Through in-depth study of KEGG.AGT(angiotensin)and CREB1(cyclic AMP response element binding protein 1)with higher Degree of Degree were found.),EDN1(endothelin-1),REN(renin)and other genes are enriched in the signal regulation pathway of upper renin secretion,regulating the secretion of renin by regulating disease targets on the signaling pathway of renin secretion.And in the endometrium,to achieve the purpose of treatment of recurrent miscarriage.Research two:Clinical Observation of Bushen Zhuyun Recipe Pre-pregnancy Intervention for Recurrent Abortion1.Research methods:A randomized controlled method was used to select 60 patients with renal spleen deficiency syndrome who were diagnosed as having luteal dysfunction in recurrent spontaneous abortion,and 30 patients in the treatment group.Pre-pregnancy intervention before taking tonifying kidney for 3 months;30 patients in the group,before the pregnancy,did not take Chinese medicine before pregnancy intervention;both groups were given Bushen Antai Recipe after pregnancy(some patients need to add progesterone capsules according to the progesterone level)to prevent pregnancy to 12 weeks of pregnancy.The curative effect was observed from the aspects of pregnancy outcome,degree of threatened abortion,serum chorionic gonadotropin,progesterone level,and follow-up neonatal health.2.Research results:(1)Comparison of pregnancy outcomes between the two groups:the total effective rate was 90.0%in the treatment group and 66.67%in the control group.The effective rate of the treatment group was significantly higher than that of the control group(P<0.05).(2)By following the follow-up of the health status of the newborn after delivery,it is suggested that the Chinese medicine is safe.Conclusion:(1)According to the results of network pharmacology,the effective active ingredients in Bushen Zhuyun Recipe can play a role in the treatment of recurrent spontaneous abortion through various pathways such as disease target,gene function and metabolic pathway.(2)It is further confirmed by clinical observation that the pre-pregnancy intervention of traditional Chinese medicine can significantly improve the success rate of post-pregnancy abortion,effectively prevent the recurrence of spontaneous abortion,and significantly improve the pregnancy outcome of patients.(3)This study provides a practical reference for clinical research and drug mechanism research of recurrent spontaneous abortion.It also provides some evidence for the scientific effectiveness of the method and lays a foundation for the development of new drugs in the future.(4)Because network pharmacology is limited by literature and database,research still has certain limitations,and further research such as animal experiment verification is needed.Due to limited personal study time,the number of sample cases collected is limited.It is hoped that in the future research,multi-center,large-sample research will be carried out to further carry out clinical research and promotion.