Hebei Key Laboratory of Integrative Medicine on Liver-kidney Patterns, College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China.
Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
J Ethnopharmacol. 2022 Jan 10;282:114580. doi: 10.1016/j.jep.2021.114580. Epub 2021 Aug 30.
Xiaoyao powder (XYP) is a traditional Chinese medicine formula which has wide scope of indications related to liver stagnation, reconcile qi and blood in TCM syndrome. Infertility can induce similar symptoms and signs to the clinical features of liver stagnation syndrome, the treatment of infertility by soothing the liver is obvious. XYP can increase the clinical pregnancy rate, follicle development, oocyte quality and improve endometrial receptivity. However, its underlying pharmacological mechanism of improving endometrial receptivity is unclear.
The aim of the study was to investigate the effect of XYP on pregnancy rates and endometrial angiogenesis, to determine the potent mechanism in association with the pro-angiogenic behavior which closely related to improving endometrial receptivity.
We established an animal model exhibiting decreasing endometrial receptivity by controlled ovarian hyperstimulation and a human endometrial microvascular endothelial cell (HEMEC) model. Endometrial morphology was observed by hematoxylin-eosin staining and Scanning electron microscopy. Western blot and qRT-PCR analysis were used to detect expression of PCNA, Cyclin D1, MMP9 and MAPK signaling pathway. Scratch-wound assay and tube formation assay were used to observe HEMEC migration and tubulogenesis.
The results demonstrated that XYP pretreatment could improve endometrial receptivity, which leads to high pregnancy rates. In the endometrium, XYP facilitated angiogenesis by promoting tube formation. XYP could enhance HEMEC proliferation and migration induced by VEGF, which were observed by the microscope and Scratch-wound assays. XYP promoted HEMEC proliferation and migration via the p38 and JNK MAPK signaling pathways.
XYP promotes HEMEC proliferation and migration via the P38 and the JNK MAPK signaling pathways, which contribute to the endometrial angiogenesis mediated by VEGFR-2 that is favorable for endometrial receptivity. We firstly elucidated the molecular mechanisms by which XYP improved endometrial receptivity by promoting angiogenesis.
逍遥散（XYP）是一种中药方剂，具有广泛的适应症，与中医的肝气郁结、气血调和有关。不孕可引起与肝气郁结综合征相似的症状和体征，疏肝治疗不孕效果明显。XYP 能提高临床妊娠率、卵泡发育、卵母细胞质量，改善子宫内膜容受性。然而，其改善子宫内膜容受性的潜在药理机制尚不清楚。
本研究旨在探讨 XYP 对妊娠率和子宫内膜血管生成的影响，确定与促进血管生成行为相关的潜在机制，这种行为与改善子宫内膜容受性密切相关。
我们建立了通过控制性卵巢过度刺激导致子宫内膜容受性降低的动物模型和人子宫内膜微血管内皮细胞（HEMEC）模型。通过苏木精-伊红染色和扫描电子显微镜观察子宫内膜形态。采用 Western blot 和 qRT-PCR 分析检测 PCNA、Cyclin D1、MMP9 和 MAPK 信号通路的表达。划痕试验和管形成试验用于观察 HEMEC 的迁移和管状形成。
结果表明，XYP 预处理可改善子宫内膜容受性，从而提高妊娠率。在子宫内膜中，XYP 通过促进管形成促进血管生成。XYP 可增强 VEGF 诱导的 HEMEC 增殖和迁移，这可通过显微镜和划痕试验观察到。XYP 通过 p38 和 JNK MAPK 信号通路促进 HEMEC 的增殖和迁移。
XYP 通过 p38 和 JNK MAPK 信号通路促进 HEMEC 的增殖和迁移，这有助于 VEGFR-2 介导的子宫内膜血管生成，有利于子宫内膜容受性。我们首次阐明了 XYP 通过促进血管生成改善子宫内膜容受性的分子机制。
