基于网络药理学和实验验证,探索加味五通灵方治疗子宫内膜异位症相关疼痛的作用机制。

Y U Siyun, Zhang Shiwen, Xia Yu, Liu Xiaoqing, Liu Yajie, F U Jinrong
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引用次数: 0

摘要

目的通过网络药理学研究和实验验证,探讨加味五通灵方(JWPTL)治疗子宫内膜异位症相关疼痛的作用和机制:方法:从公共数据库中收集加味五通灵方的有效成分、相关靶点以及子宫内膜异位症相关疼痛基因。通过蛋白-蛋白相互作用(PPI)网络工作、基因本体(GO)和京都基因组百科全书(KEGG)功能富集分析,预测 JWPTL 对抗子宫内膜异位症相关疼痛的核心靶点和通路。利用自体内膜移植法构建了Sprague-Dawley大鼠内膜异位症模型,并将成功建模的大鼠随机分为模型组和JWPTL组,每组8只。另设 8 只大鼠为假组。JWPTL组大鼠采用直肠给药法,添加JWPTL(7.77 g-kg-1-d-1),每天一次,持续28天;模型组和假手术组大鼠采用相同的给药方法,给予等量的生理盐水。在不同的时间点测量大鼠 50%的爪退缩阈值(PWT)。干预后,通过免疫组织化学和反转录聚合酶链反应检测子宫内膜组织中磷脂酰肌醇3-激酶(PI3K)和蛋白激酶B(Akt)蛋白和mRNA的表达:从GeneCards、Online Mendelian Inheritance in Man等数据库中筛选出与子宫内膜异位症(EMs)相关的疼痛靶点964个,其中JWPTL有效成分142个,靶点605个,通过维恩图交叉得到221个潜在靶点;通过构建PPI网络确定了44个核心靶点。KEGG富集分析表明,JWPTL在治疗电磁相关疼痛中主要涉及PI3K-Akt信号通路、雌激素信号通路、缺氧诱导因子-1信号通路、肿瘤坏死因子信号通路等信号通路。动物实验表明,JWPTL能上调模型大鼠异位子宫内膜组织的机械痛阈,降低PI3K和Akt蛋白及mRNA的表达:本研究初步分析了该方剂的药理机制,分子对接和动物实验表明了该研究的可行性,提示该方剂可通过下调PI3K/Akt信号通路,抑制炎症因子的释放,逆转EMs相关疼痛。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Network-based pharmacology and experimental validation to explore the mechanism of action of the Jiawei Pentongling formula for the treatment of endometriosis-related pain.

Objective: To investigate the effects and mechanisms of the Jiawei Pentongling formula (, JWPTL) in treating endometriosis-related pain using network pharmacology study and experimental validation.

Methods: Active ingredients and relevant targets of JWPTL, as well as genes for endometriosis-related pain, were collected from public databases. Prediction of core targets and pathways of JWPTL against pain associated with endometriosis by protein-protein interaction (PPI) network work, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis. The Sprague-Dawley rat endo-metriosis model was constructed using the autologous endosomal transplantation method, and the successfully modeled rats were randomly divided into the model group and the JWPTL group, with 8 rats in each group. Another 8 rats were set up in the sham group. Rats in the JWPTL group used the rectal delivery method with the addition of JWPTL (7.77 g·kg-1·d-1) once a day for 28 d. Rats in the model and sham-operated groups were given equal amounts of saline using the same administration method. The 50% paw withdrawal threshold (PWT) of the rats was measured at different time points. After the intervention, the expression of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) proteins and mRNA in endometriotic tissues was detected by immune-ohistochemistry and reverse transcription-polymerase chain reaction.

Results: From GeneCards, Online Mendelian Inheritance in Man and other databases, a total of 964 endometriosis (EMs) -related pain targets were screened, 142 active ingredients of JWPTL, 605 targets, and 221 potential targets were obtained by intersection of Venn diagram; 44 core targets were identified by constructing PPI network. KEGG enrichment analysis showed that JWPTL mainly involves the PI3K-Akt signaling pathway, estrogen signaling pathway, hypoxia inducible factor-1 signaling pathway, tumour necrotizing factor signaling pathway, and other signaling pathways in the treatment of EMs-related pain. Animal experiments showed that JWPTL could up-regulate the mechanical pain threshold and reduce the expression of PI3K and Akt proteins and mRNA in ectopic endometrial tissues of model rats.

Conclusions: The present study preliminarily analyzed the pharmacological mechanism of the formula, and molecular docking and animal experiments showed the feasibility of this study, suggesting that the formula may inhibit the release of inflammatory factors and reverse the pain associated with EMs by downregulating the PI3K/Akt signaling pathway.

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