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王志洲,邹德宝,石威,姜红江.基于网络药理学和实验验证探讨淫羊藿苷经MAPK信号通路防治激素性股骨头坏死的作用机制[J].湖南中医药大学学报英文版,2022,42(10):1749-1756.[Click to copy
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| 基于网络药理学和实验验证探讨淫羊藿苷经MAPK信号通路防治激素性股骨头坏死的作用机制 |
| 王志洲,邹德宝,石威,姜红江 |
| (安徽中医药大学, 安徽 合肥 230000;山东省文登整骨医院, 山东 威海 264400) |
| 摘要: |
| 目的 通过网络药理学结合药理实验验证探析淫羊藿苷（icariin, ICA）通过MAPK信号通路防治激素性股骨头坏死（steroid-induced avascular necrosis of the femoral head, SANFH）的作用机制。方法 基于PharmMapper数据库预测ICA的潜在靶点并借助UniProt数据库进行蛋白质标准化；从OMIM、GeneCards、DisGeNET数据库获取SANFH的靶点，借助STRING平台对ICA-SANFH共同靶点构建PPI网络图并运用Cytoscape软件进一步挖掘出更为重要的靶点；利用DAVID数据库进行GO和KEGG分析，并使用Cytoscape软件构建“靶点-通路”图。24只SPF级雌性SD大鼠随机均分为空白组、模型组及ICA组，通过激素联合脂多糖构建SANFH模型，连续灌胃8周。Micro-CT定量分析股骨头骨参数，Western blot检测p-ERK1、p-p38、p-JNK蛋白的表达。结果 得到ICA靶点226个，SANFH相关靶点677个，核心靶点ALB、AKT1、MAPK9、IGF1、EGFR等通过癌症、MAPK、PI3K-Akt等信号通路参与调控SANFH。药理实验验证结果显示：与空白组相比，模型组大鼠BMD、Tb.Th、Tb.N、Tb.Sp、p-ERK1、p-p38、p-JNK蛋白差异具有统计学意义(P<0.05)；与模型组相比，ICA组大鼠BMD、Tb.Th、Tb.N、Tb.Sp、p-ERK1、p-p38、p-JNK蛋白差异具有统计学意义(P<0.05)。结论 本次研究证实了ICA经MAPK信号通路治疗SANFH的作用机制，具有一定的应用价值。 |
| 关键词: 网络药理学 药理实验 淫羊藿苷 激素性股骨头坏死 MAPK通路 作用机制 |
| DOI：10.3969/j.issn.1674-070X.2022.10.026 |
| Received:June 17, 2022 |
| 基金项目:山东省中医药科技发展计划项目（2019-0798）；威海市组织工程与再生医学重点实验室研究项目;威海市第四批中医重点专科建设项目（骨关节科）（威卫办〔2019〕87号）。 |
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| Investigating the mechanism of icariin to prevent and treat steroid-induced avascular necrosis of the femoral head through MAPK signaling pathways based on network pharmacology and experimental verification |
| WANG Zhizhou,ZOU Debao,SHI Wei,JIANG Hongjiang |
| (Anhui University of Chinese Medicine, Hefei, Anhui 230000, China;Shandong Wendeng Osteopathic Hospital, Weihai, Shandong 264400, China) |
| Abstract: |
| Objective To investigate the mechanism of icariin (ICA) in preventing and treating steroid-induced avascular necrosis of the femoral head through MAPK signaling pathways based on network pharmacology and experimental verification. Methods Potential targets of ICA were predicted based on PharmMapper database and protein standardization was carried out by UniProt database. The targets of SANFH were obtained from OMIM, GeneCards and DisGeNET databases. The protein-protein interaction (PPI) network map of ICA-SANFH common targets was constructed with STRING platform, and more important targets were further mined by Cytoscape 3.9.1 software. DAVID database functioned to perform gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis, and Cytoscape software worked to draw the "target-pathway" maps. Besides, 24 SPF female SD rats were randomly divided into the blank group, model group and ICA group. The SANFH model with hormone and lipopolysaccharide was constructed and received the gavage for 8 weeks. We obtained the femoral head bone parameters by Micro-CT quantitative analysis, and detected the expressions of p-ERK1, P-P38, P-JNK proteins by the western-blot. Results We obtained 226 ICA targets and 677 SANFH-related targets, among which, ALB, AKT1, MAPK9, IGF1, EGFR and other core targets were involved in the regulation of SANFH through cancer, MAPK, PI3K-Akt and other signaling pathways. From the pharmacological experiment, we found significant difference in BMD, Tb.Th, Tb.N, Tb.Sp, p-ERK1, p-p38, p-JNK proteins between the blank group and model group (P<0.05). Moreover, there existed significant difference in BMD, Tb.Th, TB.N, TB.Sp, p-ERK1, p-p38 and p-JNK proteins between the model group and ICA group (P<0.05). Conclusion The mechanism of ICA in the treatment of SANFH through MAPK signaling pathway was verified, which could be applied in practice. |
| Key words: network pharmacology pharmacological experiment icariin steroid-induced avascular necrosis of the femoral head MAPK pathway mechanism of action |
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