摘要
目的基于网络药理学分析黄五甘附膏缓解膝骨关节炎(KOA)疼痛的作用机制,并进行动物实验验证。方法通过TCMSP、PubChem数据库和SwissADME平台获取黄五甘附膏药物活性成分并筛选有效成分;通过SEA数据库获取药物有效成分靶点,通过GeneCards、OMIM等数据库获取KOA疾病相关靶点,并取二者交集;运用Cytoscape3.9.0软件构建有效成分-靶点-疾病网络;通过STRING数据库构建蛋白相互作用(PPI)网络,并筛选核心靶点;通过DAVID平台对交集靶点进行GO和KEGG通路富集分析。建立KOA寒湿证大鼠模型,采用黄五甘附膏对其进行干预,观察药效并检测核心靶点表达。结果从黄五甘附膏中筛选出有效成分104个,得到59个治疗KOA的潜在作用靶点;通过PPI网络分析得到重要靶点有IL6、IL1B、PTGS2等;KEGG通路富集分析结果显示可能涉及IL-17、TNF、TRP、NF-κB等84条信号通路,多与炎症有关。动物实验显示,模型大鼠Lecuesne MG评分升高(P<0.05),缩足阈值(PWT)明显降低(P<0.05);与模型组比较,黄五甘附膏中、高剂量组大鼠PWT明显恢复,滑膜炎Krenn评分降低(P<0.05),黄五甘附膏高剂量组软骨组织Mankin评分降低(P<0.05),黄五甘附膏各剂量组血清IL-6、IL-1β含量降低(P<0.01),黄五甘附膏中、高剂量组TRPV1蛋白表达下调(P<0.05,P<0.01)。结论黄五甘附膏缓解KOA疼痛机制可能与减轻炎性反应,减少炎性因子IL-1β、IL-6释放,进而缓解KOA炎性痛敏,下调TRPV1表达有关。
Objective To analyze the mechanism of Huangwu Ganfu Ointment in relieving pain of knee osteoarthritis(KOA)based on network pharmacology;To verify it in animal experiments.Methods The active components of Huangwu Ganfu Ointment were obtained by TCMSP database,PubChem database and SwissADME platform,the effective components were screened,and the targets were obtained from SEA database.KOA diseaserelated targets were obtained from GeneCards,OMIM and other databases,and the intersection targets were obtained.A effective component-target-disease network was constructed using Cytoscape 3.9.0 Software.Protein-protein interaction(PPI)network was constructed by STRING database and core targets were screened.GO and KEGG enrichment analysis of intersection targets were analyzed using DAVID platform.The KOA rat model with cold and damp syndrome was established,and the intervention of Huangwu Ganfu Ointment was carried out.The efficacy was observed and the core target expressions were detected.Results Totally 104 effective components were screened from Huangwu Ganfu Ointment,and 59 potential targets were obtained for treating KOA.PPI network interaction analysis obtained the important targets of IL6,IL1B and PTGS2.KEGG enrichment results showed that Huangwu Ganfu Ointment may involve 84 signaling pathways such as IL-17,TNF,TRP and NF-κB in the treatment of KOA,most of which were related to inflammation.The results of animal experiments showed that Lecuesne MG scores increased in the model rats(P<0.05),and paw withdrawal threshold(PWT)significantly decreased(P<0.05).Compared with model group,PWT in Huangwu Ganfu Ointment medium-and high-dosage groups were significantly recovered,and synovitis Krenn score decreased(P<0.05).The Mankin score of cartilage tissue of Huangwu Ganfu Ointment high-dosage group decreased(P<0.05).The contents of IL-6 and IL-1βin all Huangwu Ganfu Ointment groups decreased(P<0.01).Huangwu Ganfu Ointment medium-and high-dosage groups could down-regulate the expression of TRPV1 protein(P<0.05,P<0.01).Conclusion The mechanism of Huangwu Ganfu Ointment in alleviating the pain of KOA may be related to reducing inflammatory response,reducing the release of inflammatory factors of IL-1βand IL-6,alleviating inflammatory pain sensitivity of KOA,and down-regulating the expression level of TRPV1.
作者
姜楚洋
王兆南
李家豪
青千裕
赵乐
赵子苇
李艳彦
JIANG Chuyang;WANG Zhaonan;LI Jiahao;QING Qianyu;ZHAO Le;ZHAO Ziwei;LI Yanyan(Shanxi University of Chinese Medicine,Jinzhong 030619,China;Affiliated Hospital of Shanxi University of Chinese Medicine,Taiyuan 030024,China)
出处
《中国中医药信息杂志》
CAS
CSCD
2024年第1期20-28,共9页
Chinese Journal of Information on Traditional Chinese Medicine
基金
山西省研究生教育创新项目(2022Y718)
山西中医药大学研究生创业项目(2022CX020)。
