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基于网络药理学和动物实验探究逍遥丸治疗骨质疏松症作用机制OA北大核心CSTPCD

Exploring the mechanism of action of Xiaoyao pill in the treatment of osteoporosis based on network pharmacology and animal experiments

中文摘要英文摘要

目的:基于网络药理学并通过动物实验研究逍遥丸对去卵巢骨质疏松症中小鼠骨结构形态的治疗作用,以及对AGES/RAGE信号转导途径的改变和分子机制.方法:通过TCMSP等数据库搜索逍遥丸药物成分及其成分相关靶点;以"osteoporosis"为关键词,在GeneCards等数据库搜索骨质疏松症相关的靶点;制作韦恩图,获取交集靶点;最后通过DAVID数据库,对药物-疾病交集靶点进行GO与KEGG富集分析并将富集结果可视化.其次,建立小鼠骨质疏松模型,通过CT扫描,HE染色以及免疫组化等检测逍遥丸对成骨分化的影响,并验证网络药理学信号通路预测结果.结果:逍遥丸治疗骨质疏松症的核心活性成分有8种,分别为柴胡、当归、白芍、炒白术、茯苓、炙甘草、薄荷、生姜,合并去重后共得到225个靶点基因.其关键靶点主要参与调控AGEs/RAGE信号通路、IL-17信号通路、TNF 信号通路等.在小鼠骨质疏松模型中,逍遥丸能有效提高ALP、COL-1成骨转录因子表达(P<0.05),同时下调 AGEs/RAGE 信号通路关键蛋白rage、IL-6 的表达(P<0.05).结论:逍遥丸有效改善去卵巢骨质疏松症小鼠骨形态学结构,具有抗去卵巢骨质疏松作用,其机制可能与抑制AGES/RAGE信号通路,提高成骨标志基因ALP、COL-1有关.

Objective:To investigate the therapeutic effects of Xiaoyao pill on bone structure and morphology in mice with ovariectomy-induced osteoporosis,as well as the changes and molecular mechanism of AGES/RAGE signaling pathway based on network pharmacology and animal experiments.Methods:TCMSP and other databases were used to search for the drug ingredi-ents of Xiaoyao pill and their related targets."Osteoporosis"was used as the keyword in GeneCards and other databases to search for osteoporosis disease-related targets;Wayne diagrams were made to obtain intersection targets;Finally,GO and KEGG enrich-ment analyses were performed on drug-disease intersection targets through DAVID database,and the enrichment results were vi-sualized.Additionally,mice model with ovariectomy-induced osteoporosis were established,and the influence of Xiaoyao pill on osteogenic differentiation was detected by CT scanning,HE staining and immunohistochemistry,and the prediction results of net-work pharmacological signaling pathways were verified.Results:Eight core active ingredients in Xiaoyao pill were found,namely chaihu,angelica,white peony,fried baiju,poria,licorice,peppermint and ginger.A total of 225 key targets of Xiaoyao Pill and OP were predicted,and these key targets were mainly involved in regulating the AGEs/RAGE signaling pathway,IL-17 signal-ing pathway,TNF signaling pathway,etc.In the mouse osteoporosis model,Xiaoyao pill could effectively increase the expression of ALP and COL-1 osteogenic transcription factors(P<0.05),and downregulate the expression of rage and IL-6,key proteins of the AGEs/RAGE signaling pathway(P<0.05).Conclusion:Xiaoyao pill can effectively improve the bone morphological struc-ture in mice with osteoporosis and has anti-ovary osteoporosis effect,and its mechanism may be related to inhibition of AGES/RAGE signaling pathway and increase osteogenic marker genes ALP and COL-1.

旷珊珊;张耀文;赵娜;杨艺欣;解继胜

右江民族医学院,广西 百色 533000

中医学

绝经后骨质疏松症逍遥丸网络药理学信号通路疏肝解郁

Postmenopausal osteoporosisXiaoyao pillNetwork pharmacologySignal pathwayRelieve liver depression

《海南医学院学报》 2024 (009)

683-690 / 8

This study was supported by the National Natural Science Foundation of China(81560362);Baise City Science Research and Technology Development Plan Project(20224128) 国家自然科学基金资助项目(81560362);百色市科学研究与技术开发计划项目(20224128)

10.13210/j.cnki.jhmu.20231212.001

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