基于数据挖掘、网络药理学和分子对接技术探讨中医药治疗原发性干燥综合征的用药规律和作用机制

Exploring the medication rules and mechanism of action of Chinese medicine for primary Sj gren′s syndrome based on data mining,network pharmacology and molecular docking technology

目的探究中医药治疗原发性干燥综合征的用药规律,预测核心药物的潜在作用机制。方法检索SinoMed、CNKI、WanFang Data、VIP数据库中关于中药复方治疗原发性干燥综合征的文献,构建处方数据库,运用R 4.2.0软件进行药物和性味归经频数统计、关联规则及聚类分析,得到核心药物。利用网络药理学方法绘制中药处方-活性化合物分子-核心靶点-pSS调控网络,预测核心药物的潜在作用靶点和通路,并使用分子对接技术验证核心化合物成分与核心靶点的结合能力。结果筛选得到121首治疗原发性干燥综合征的处方,涉及162味中药,前三味高频药物为麦冬、地黄、甘草,使用频次≥10次的30味高频药物以补虚药(补气药、补阴药、补血药)占比最多,其次为清热凉血、活血调经药;性味以甘、苦、寒为主,归经以肝、肺、胃、脾、肾、心经为主;关联规则分析得到核心药对组合29个;高频中药聚类分析得到5个组合。对核心药物进行网络药理学分析得到山柰酚、槲皮素、丹参酮ⅡA、甲基麦芽酮A等核心活性成分和5个核心靶点;富集分析提示主要涉及脂质与脂肪酸代谢、动脉粥样硬化通路、NADP结合、双加氧酶活性调节、白细胞跨内皮迁移等生物学过程;分子对接表明化合物配体与蛋白受体间具备良好的结合能力。结论原发性干燥综合征多以气阴两虚为本,燥热、血瘀致病,中药复方以益气养阴润燥、清热凉血活血为主;多个核心化合物成分对应的多个靶点介入氧化、白细胞迁移等生物过程产生作用。

Objective Explore the regularity of traditional Chinese medicine in the treatment of primary Sjogren′s syndrome,and predict the potential mechanism of action of core drugs.Methods Searched Sino Med,CNKI,WanFang Data,and VIP databases for the literature on the treatment of primary Sj gren′s syndrome with traditional Chinese medicines,constructed a prescription database,and used R 4.2.0 software to carry out frequency statistics,association rules,and cluster analysis of drugs,properties,and flavors,to get the core drug.Use the network pharmacology method to map the regulatory network of traditional Chinese medicine prescription-active compound molecules-core targets-pSS,predict the potential targets and pathways of core drugs,and use molecular docking technology to verify the binding ability of core compound components and core targets.Results Screened and obtained 121 prescriptions for the treatment of primary Sjogren′s syndrome,involving 162 traditional Chinese medicines,the first three high-frequency drugs are Ophiopogon japonicus,Rehmannia glutinosa,and licorice.medicines,yin-tonifying medicines,and blood-tonifying medicines accounted for the largest proportion,followed by heat-clearing and cooling blood medicines,blood-activating and menstrual-regulating medicines;the nature and flavor are mainly sweet,bitter,and cold,and the main meridians are liver,lung,stomach,spleen,kidney,and heart meridian.Association rule analysis obtained 29 combinations of core medicine pairs;cluster analysis of high-frequency traditional Chinese medicine obtained 5 combinations.Network pharmacology analysis of core drugs yielded kaempferol,quercetin,tanshinoneⅡA,methylmaltone A and other core active ingredients and 5 core targets;enrichment analysis indicated that they were mainly involved in lipid and fatty acid metabolism,atherosclerosis Sclerosis pathway,NADP binding,dioxygenase activity regulation,leukocyte transendothelial migration and other biological processes;Molecular docking shows that the compound ligand has a good binding ability with the protein receptor.Conclusion Primary Sjogren′s syndrome is mostly based on deficiency of both qi and yin,and is caused by dryness and heat and blood stasis.The traditional Chinese medicine compound is mainly based on nourishing qi,nourishing yin and moistening dryness,clearing heat,cooling blood and promoting blood circulation;multiple targets corresponding to multiple core compounds Involved in biological processes such as oxidation and leukocyte migration.