现代中西医结合杂志2025，Vol.34Issue(21)：2921-2933,13.DOI:10.3969/j.issn.1008-8849.2025.21.001
基于网络药理学、分子对接及动物实验阐释填精荣胞方治疗复发性流产合并血栓前状态的机制
Potential mechanism of Tianjing Rongbao Formula in the treatment of recurrent spontaneous abortion with prethrombotic state based on network pharmacology,molecular docking and animal experiment
摘要
Abstract
Objective It is to elucidate the mechanism of Tianjing Rongbao Formula(TJRBF)in the treatment of re-current spontaneous abortion(RSA)with prethrombotic state(PTS)based on network pharmacology,molecular docking and animal experiment.Methods ①The TJRBF's ingredients were detected by liquid chromatography-mass spectrometry technology.②The target molecules and signaling pathways involved in the therapeutic effects of TJRBF on RSA were pre-dicted by network pharmacology.③The binding affinity of key active ingredients with key targets was preliminarily evalua-ted by molecular docking.④The mechanism of TJRBF was confirmed by animal experiments.Thirty-six female CBA/J mice were randomly divided into 6 groups,with 6 mice in each group.The blank and model groups received distilled water via gavage,the aspirin group received aspirin 11.38 mg/kg via gavage,the low-,medium-,and high-dose groups of TJRBF respectively received TJRBF 6.27 g/kg,18.81 g/kg and 56.42 g/kg via gavage,all once daily.After 14 days of continuous administration,the female CBA/J mice of the control group were co-housed with male BALB/c mice to establish models of normal pregnancy,the female CBA/J mice from the remaining groups were co-housed with male DBA/2 mice to establish models of RSA with PTS.From the 1st to 14 days of gestation,each group was continuously treated with the origi-nal administration regimen.On the 15th of gestation,the samples were collected,embryo loss rate was calculated,serum levels of estradiol(E2),progesterone(P)and D-dimer(D-D)were measured,the placental histopathology was observed by HE staining,the expressions of vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor 1(VEGFR1),VEGF receptor 2(VEGFR2)in placental tissue were detected by immunohistochemistry,the protein expres-sions of leukemia inhibitory factor(LIF),Janus kinase 1(JAK1),signal transducer and activator of transcription 3(STAT3),VEGF,VEGFR1 and VEGFR2 were detected by Western blot.Results The top 20 components in TJRBF were screened out based on their relative abundance values from highest to lowest.These components were predicted to act on 153 targets in RAS,inwhich TP53,AKT1,STAT3,TNF and SRC might be the key targets,and JAK-STAT pathway might be the key pathway.The molecular docking results showed that the key ingredients could bind well with the key targets.Animal experimental results showed that the embryo loss rate and serum level of D-D in all medicated groups were signifi-cantly lower than those in the model group(all P<0.05);the serum levels of E2 and P in the aspirin group and high-dose TJRBF group,serum level of E2 in the medium-dose TJRBF group,and serum level of P in the low-dose TJRBF group were significantly higher than those in the model group(all P<0.05);the number of blood vessels in placental labyrinth were increased,while placental hemorrhage and congestion were decreased in each medicated group;the relative protein expres-sions of LIF and STAT3 in placental tissue in each medicated group,the relative protein expressions of JAK1 and VEGF in the low-dose TJRBF group,the relative protein expression of VEGF in the medium-dose TJRBF group,and the relative pro-tein expressions of JAK1 and VEGFR2 in the high-dose TJRBF group were all significantly higher than those in the model group(all P<0.05).Conclusion TJRBF had a therapeutic effect on RSA with PTS through multiple ingredients,targets and pathways,among which regulating JAK-STAT signaling pathway and up-regulating the expressions of LIF,JAK1,STAT3,VEGF and VEGFR2 in placentas may be one of the mechanisms.关键词
复发性流产/血栓前状态/填精荣胞方/网络药理学/分子对接/JAK-STAT信号通路Key words
recurrent spontaneous abortion/prethrombotic state/Tianjing Rongbao Formula/network pharmacology/molecular docking/JAK-STAT signaling pathway分类
医药卫生引用本文复制引用
ZHU Youhua,HUANG Yuxiao,ZHAO Jiajing,YANG Yanan,FANG Mengxin,BU Mengya,ZHANG Yuqing,SUN Jiaqi..基于网络药理学、分子对接及动物实验阐释填精荣胞方治疗复发性流产合并血栓前状态的机制[J].现代中西医结合杂志,2025,34(21):2921-2933,13.基金项目
中国中医科学院科技创新工程项目(CI2021A02411) （CI2021A02411）
国家自然科学基金培育项目(XY20-09) （XY20-09）
