茸脂胶囊治疗激素性股骨头坏死的网络药理学分析及动物实验*

作者：林天烨1,2，杨旭辉3，陈伯亮4，何晓铭1,2，何敏聪1,2，李子祺1,2，侯 凯4，何 伟1,2，张庆文1,2，邓 攀4

单位：1.广东省中医骨伤研究院，广东 广州 510405； 2.广州中医药大学第三附属医院，广东 广州 510405； 3.广州中医药大学第三临床医学院，广东 广州 510405； 4.宝鸡市中医医院，陕西 宝鸡 721000

引用：引用：林天烨，杨旭辉，陈伯亮，何晓铭，何敏聪，李子祺，侯凯，何伟，张庆文，邓攀.茸脂胶囊治疗激素性股骨头坏死的网络药理学分析及动物实验[J].中医药导报,2025,31(7):32-39.

DOI：10.13862/j.cn43-1446/r.2025.07.005

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摘要：

目的：基于网络药理学分析及动物实验探究茸脂胶囊治疗激素性股骨头坏死的作用机制。方法：通过中药系统药理数据库与分析平台（TCMSP）获得茸脂胶囊的潜在化学成分和靶点。利用GeneCards和OMIM数据库筛选与激素性股骨头坏死相关的基因，并用R软件实现药物靶点和疾病靶点的映射匹配。采用Cytoscape软件构建药物、成分、靶点和疾病间的可视化网络，通过String数据库在线平台构建蛋白质互作网络。将30只大鼠随机分为造模组20只和对照组10只。造模组大鼠构建激素性股骨头坏死模型，将造模成功大鼠随机分为模型组和中药组，每组10只。中药组采用茸脂胶囊灌胃，对照组、模型组大鼠均予等体积的蒸馏水灌胃。干预8周后，采用苏木精-伊红（HE）染色法观察大鼠股骨头空骨陷窝率。利用RT-qPCR检测股骨头组织CXC趋化因子受体2（CXCR2） mRNA、胱天蛋白酶-3（Caspase-3） mRNA、B细胞淋巴瘤2（Bcl-2）相关X蛋白（Bax）mRNA表达，Western blotting检测股骨头组织CXCR2、Caspase-3、Bax蛋白表达。结果：获得茸脂胶囊有效成分163种，活性成分的作用靶标578个，茸脂胶囊治疗激素性股骨头坏死145个潜在靶标。排名前5位的潜在核心靶基因分别为肿瘤蛋白53（TP53）、CXCR2、β-连环蛋白（CTNNB1）、E1A结合蛋白（EP300）、表皮生长因子受体（EGFR）。基因本体论（GO）富集分析显示生物过程（BP）主要富集于正性调节基因表达、RNA聚合酶Ⅱ介导的正性转录调节、对缺氧的反应、负性调节基因表达和正性调节白细胞介素-8（IL-8）产生等，细胞组分（CC）主要富集于细胞外空间、细胞外区域、含胶原的细胞外基质等，分子功能（MF）主要富集于酶结合、相同蛋白质结合、细胞因子活性蛋白质同源二聚化活性等。京都基因与基因百科组全书（KEGG）通路主要涉及磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）信号通路、FoxO信号通路、Toll样受体信号通路、白细胞介素-17（IL-17）信号通路、酒精性肝病等。模型组、中药组大鼠股骨头空骨陷窝率均高于对照组（P<0.05）；中药组大鼠股骨头空骨陷窝率低于模型组（P<0.05）。模型组大鼠股骨头组织CXCR2 mRNA、Caspase-3 mRNA、Bax mRNA及CXCR2、Caspase-3、Bax蛋白相对表达量均高于对照组（P<0.05）；中药组大鼠股骨头组织CXCR2 mRNA、Caspase-3 mRNA、Bax mRNA及CXCR2、Caspase-3、Bax蛋白相对表达量均低于模型组（P<0.05）。结论：茸脂胶囊可通过多成分、多靶点途径治疗激素性股骨头坏死；CXCR2是茸脂胶囊治疗激素性股骨头坏死的核心靶标；茸脂胶囊可抑制激素性股骨头坏死大鼠骨细胞凋亡，从而达到治疗激素性股骨头坏死的作用。

关键词：激素性股骨头坏死；茸脂胶囊；网络药理学；CXC趋化因子受体2；分子机制；大鼠

Abstract：

Objective: To explore the mechanism of action of Rongzhi capsules in treating steroid-induced osteonecrosis of the femoral head based on network pharmacology analysis and animal experiments. Method: The potential chemical composition and target prediction of Rongzhi capsules were obtained through the traditional Chinese medicine pharmacology database and analysis platform (TCMSP) database. GeneCards and OMIM databases were used to screen genes related to steroid-induced osteonecrosis of the femoral head, and R software was applied to achieve mapping and matching of drug targets and disease targets. On this basis, a visualization network of drugs, ingredients, targets, and diseases was constructed using Cytoscape software, and a protein interaction network was constructed using the String database online platform. In addition, 30 rats were randomly divided into modeling group (n=20) and control group (n=10). A rat model of steroid-induced osteonecrosis of the femoral head was constructed in modeling group, and the successful model rats were randomly divided into model group and Chinese medicine group, 10 rats in each group. The Chinese medicine group was administered with Rongzhi capsules by gavage, while the control group and model group rats were given equal volumes of distilled water by gavage. Hematoxylin eosin (HE) staining method was used to observe empty bone cavity rate in rat femoral head in 8 weeks. At the same time, RT qPCR was used to detect the expression of CXC chemokine receptor 2 (CXCR2) mRNA, Caspase-3 mRNA, and Bcl-2 related X protein (Bax) mRNA in the femoral head of rats. Western blotting techniques was used to detect the protein expression of CXCR2, Caspase-3 and Bax in the femoral head of rats. Result: Totally 163 effective ingredients of Rongzhi capsules were collected, and 578 potential targets for the active ingredients of Rongzhi Capsules were predicted, with 145 potential targets for the treatment of femoral head necrosis. The top 5 potential core target genes were identified as TP53, CXCR2, CTNNB1, EP300 and EGFR. Gene ontology (GO) analysis shows that its biological processes (BP) were mainly enriched in positive regulation of gene expression, RNA polymerase Ⅱ mediated positive transcription regulation, response to hypoxia, negative regulation of gene expression, and positive regulation of interleukin-8(IL-8) production. Its cellular components (CC) were mainly enriched in extracellular space, extracellular regions, collagen containing extracellular matrix, etc. Its molecular functions (MF) were mainly enriched in enzyme binding, homologous protein binding, cytokine active protein homodimerization activity, etc. The Kyoto encyclopedia of genes and genomes (KEGG) pathway mainly involved phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, FoxO signaling pathway, toll like receptor signaling pathway, interleukin-17(IL-17) signaling pathway, alcoholic liver disease, etc. The Chinese medicine group and model group showed higher empty bone pit rate of the femoral head than control group (P<0.05). The Chinese medicine group showed lower empty bone pit rate of the femoral head than model group (P<0.05). The model group showed higher expression of CXCR2 mRNA, Caspase-3 mRNA, Bax mRNA and CXCR2, Caspase-3, Bax protein than control group (P<0.05). The Chinese medicine group showed lower expression of CXCR2 mRNA, Caspase-3 mRNA, Bax mRNA and CXCR2, Caspase-3, Bax protein than model group (P<0.05). Conclusion: The characteristics of the therapeutic effect of Rongzhi capsules on steroid-induced osteonecrosis of the femoral head are multi-component and multi-target. CXCR2 is the core target of Rongzhi capsules in treating steroid-induced osteonecrosis of the femoral head. Rongzhi capsules can inhibit the apoptosis of bone cells in rats with steroid-induced osteonecrosis of the femoral head, thereby achieving the therapeutic effect of treating steroid-induced osteonecrosis of the femoral head.

Key words：steroid-induced osteonecrosis of the femoral head; Rongzhi capsules; network pharmacology; CXC chemokine receptor 2; molecular mechanisms; rat

发布时间：2026-01-06

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