基于数据挖掘和网络药理学的慢性肾小球肾炎用药规律和作用机制研究

Research on the Medication Rule and Mechanism of Action of Chronic Glomerulonephritis Based on Data Mining and Network Pharmacology

目的 运用数据挖掘和网络药理学的研究方法,探讨中药在慢性肾小球肾炎(chronic glomerulonephritis,CGN)治疗中的组方规律和作用机制,为其治疗提供参考。方法 以在中国知网(CNKI)、中国生物医学文献数据库、万方数据(Wanfang)、维普中文期刊(VIP)等数据库中检索到的、在1979年至2021年9月发表的中药复方治疗CGN的文献为数据来源,采用中医传承辅助平台对其进行频次和关联规则分析,研究治疗CGN药物的组成规律,并在此基础上采用网络药理学的研究方法,筛选核心靶点并通过KEGG通路和GO功能富集分析,研究高频药物与疾病的潜在作用靶点,阐明其作用机制。结果 共计732篇文献符合检索条件,包含296味中药,发现20味使用超过100次的高频药物,补虚药、利水渗湿药、活血化瘀药应用较多;药物性味以温、苦为主,归脾经、肝经、肾经较多;进一步关联分析得到高频药对(药组)12个;核心处方4个。应用网络药理学的研究方法,对核心药组“黄芪、白术、茯苓、山药”的作用机制进行探索,发现其主要活性成分槲皮素、山萘酚、芒柄花黄素等主要作用于核因子-κB亚基RELA、蛋白激酶B、细胞周期蛋白依赖性激酶Ⅱ、肿瘤抑制因子、雌激素受体1等核心靶点,通过晚期糖基化终末产物-晚期糖基化终产物受体、癌症、核因子-κB、缺氧诱导因子等信号通路,以及氧化应激、炎症反应、凋亡的负向调控等生物过程发挥治疗作用。结论 中药治疗CGN常以益气、健脾、温肾治其本,利水渗湿、活血化瘀治其标。高频药物可能是通过调控炎症、氧化应激与凋亡等信号通路发挥治疗作用。

Objective To explore the prescription rule and mechanism of action of traditional Chinese medicine(TCM) in the treatment of chronic glomerulonephritis(CGN)by using data mining and network pharmacology research methods,and to provide reference for the prevention and treatment of CGN. Methods Using the literatures on the treatment of CGN with TCM compounds,which were retrieved from the databases of CNKI,CBM,WanFang and VIP from 1979 to September 2021 as the data sources,we conducted frequency analysis and association rule analysis using TCMISS and studied the composition rules of prescriptions for the prevention and treatment of CGN.Then network pharmacology methods were used to screen core targets,KEGG pathway and gene ontology enrichment analysis were used for further research on potential targets of high-frequency drugs and disease. Subsequently,the underlying mechanism was illustrated. Results A total of 732 documents met the search criteria, including 296Chinese medicines. It had been found that 20 high-frequency Chinese medicines were used more than 100 times.The drugs mainly focused on tonic for deficiency, diuretic for dampness, and activator of blood circulation and blood stasis. The medicinal flavors were mainly warm and bitter,which belonged to the spleen,liver and kidney channels. Further correlation analysis yielded 12 high-frequency drug pairs(drug groups)and 4 core prescriptions.By applying the network pharmacology research method,the mechanism of action of the core drug group “Astragali Radix, Atractylodis Macrocephalae Rhizoma, Poria and Dioscoreae Rhizoma” was explored. The main active ingredients in core drug group(including quercetin,kaempferol and formononetin)were found to mainly act on key targets, such as nuclear factor-κB RELA,protein kinase B(PKB),cyclin dependent kinase II(CDK2),tumor suppressor and estrogen receptor1(ESR1),and to exert therapeutic effects through activating signaling pathways,such as advanced glycation end products-receptor of advanced glycation end products(AGE-RAGE), cancer,nuclear factor-κB(NF-κB), hypoxia inducible factor(HIF), and negatively regulating biological processes,including oxidative stress, inflammatory response, and apoptosis. Conclusions TCM in the treatment of CGN mainly focuses on replenishing qi,strengthening the spleen,and warming the kidneys,and promoting diuresis and eliminating dampness, activating blood circulation, and removing blood stasis to treat the symptoms. Highfrequency drugs may exert their therapeutic effects through regulating signal pathways related to inflammation,oxidative stress,and apoptosis.