Difference in Network Mechanism of Shoutaiwan and Juyuanjian in Reversing Pathology of Decidua of Spontaneous Abortion Patients： Based on "Uterine Collaterals Connecting Kidney" and "Fetal Collaterals Connecting Spleen" Theory / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo explore difference in the mechanism of Shoutaiwan， a representative kidney-tonifying and abortion-preventing formula， and Juyuanjian， a typical spleen-invigorating and abortion-preventing formula in reversing the pathology of decidua of spontaneous abortion （SA） patients and to expound the connotation of "uterine collaterals connecting kidney" and "fetal collaterals connecting spleen" theory. MethodThe targets of SA were retrieved from GeneCards， followed by gene ontology-biological process （GO-BP） annotation. Based on Cytoscape and previous research， the main processes and core targets were screened out. High-performance liquid chromatography-mass spectrometry （HPLC-MS） was used to identify the potential active components of Shoutaiwan and Juyuanjian and the regulatory networks were constructed. SA was induced in rats and the model rats were treated with Shoutaiwan and Juyuanjian at the same unit. Hematoxylin and eosin （HE） staining， transmission electron microscopy （TEM）， enzyme-linked immunosorbent assay （ELISA）， immunohistochemistry （IHC）， immunofluorescence （IF）， and other methods were employed to verify the mechanisms against miscarriage. ResultThe dysregulation of cell adhesion， inflammatory response， cell death， and angiogenesis was the core pathological process of SA. A total of 13 potential specific active components of Shoutaiwan and 14 active components of Juyuanjian were screened out. The regulatory networks showed that the potential active components of the two prescriptions modulated vascular endothelial growth factor （VEGF）， interleukin （IL）-2， estrogen receptor （ESR）-1， matrix metalloproteinase-9 （MMP-9）， and other targets to regulate the pathological process of SA. The two can significantly improve the pregnancy rate and the integrity rate and blood supply of decidua cells， control the apoptosis morphology and the expression of estrogen （E2）， progesterone （P）， and its receptor， and down-regulate the expression of MMP-2， MMP-9， IL-2， and IL-6 in decidua tissue of SA rats. At the same time， they up-regulated the expression of anti-apoptotic protein B-cell lymphoma-2 （Bcl-2） and IL-4. Shoutaiwan significantly up-regulated the expression of VEGF， and Juyuanjian significantly down-regulated the expression of E-cadherin （E-Cad）. ConclusionBoth Shoutaiwan and Juyuanjian regulate the core pathological process of SA to prevent miscarriage. At the same unit， Shoutaiwan is overall superior to Juyuanjian. Shoutaiwan is better than Juyuanjian in regulating angiogenesis and Juyuanjian is superior to Shoutaiwan in regulating cell adhesion. This conclusion can partly explain the biological basis of "treating the same disease with different methods"， and provide objective data reference for the identification of quality marker （Q-marker） of anti-miscarriage Chinese medicine and further study of formula-syndrome metabolome.