目的 探讨在真实世界中鹿瓜多肽注射液治疗骨关节炎的人群特征及联合用药情况，并通过构建靶点网络预测其作用机制。方法 通过调取医院信息系统（hospital information systeam，HIS）数据库中使用过鹿瓜多肽注射液治疗骨关节炎患者信息，使用SAS9.2及R软件对其使用人群特征及用药情况进行统计；通过分析应用鹿瓜多肽注射液的骨关节炎患者的治疗结局以判断其有效性，并与未使用鹿瓜多肽的骨关节炎患者的治疗结局进行对比分析；Clementine 12.0对联合用药情况进行关联规则分析，并按照置信度排序；利用CNKI、TCMSP数据库及Cytoscape软件构建“疾病-药物-成分-靶点”网络及蛋白相互作用网络，并进行拓扑学分析筛选核心成分与核心靶点；将药物靶点与疾病靶点的交集靶点进行基因本体（gene ontology，GO）及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）富集分析；最后将核心成分与核心靶点进行分子对接。结果 4050例骨关节炎患者中，46～65岁年龄段最多（2248例，55.51%），其次为66～75岁年龄段（850例，20.99%），其中女性患者占多数（2657例，70.35%）。4050例应用鹿瓜多肽注射液治疗的骨关节炎患者的总有效率为97.88%，对比未应用鹿瓜多肽注射液的骨关节炎患者的治疗效果，显示鹿瓜多肽注射液疗效更好。关联规则显示鹿瓜多肽注射液治疗骨关节炎常与激素（倍他米松）、抗生素（头孢唑啉）、抗炎镇痛药（骨肽注射剂）、补肾壮骨剂（金天格胶囊）、活血化瘀剂（脉血康胶囊）合并用药。靶点网络分析得到核心成分棕榈酸、肉豆蔻酸、色氨酸、维生素A等10种；核心靶点过氧化物酶体增殖物激活受体（peroxisome proliferator-activated receptor gamma，PPARG）、髓过氧物酶（myeloperoxidase，MPO）、受体型酪氨酸蛋白磷酸酶C（receptor-type tyrosine-protein phosphatase C，PTPRC）等9个，其中分子对接较好的组合：维生素A与丝裂原活化蛋白激酶14（mitogen-activated protein kinase 14，MAPK14）、色氨酸与基质金属蛋白酶9（matrix metalloproteinase 9，MMP9）、维生素A与PTPRC。GO及KEGG分析结果显示，主要涉及免疫炎症、激素分泌、血液循环及MAPK通路等方面。结论 鹿瓜多肽治疗骨关节炎的患者主要为女性中老年人，其常见证型为肝肾亏虚、湿热及气滞血瘀证；其中药治疗多联合补肾壮骨剂、活血化瘀剂以求标本同治，而化学药治疗常对症治疗以缓解症状。通过靶点网络构建与分析则得出鹿瓜多肽主要通过维生素A及氨基酸对MMP9、MPO等靶点进行调控从而发挥作用。

Objective To explore the characteristics of the population and combination of drugs in the real world for the treatment of osteoarthritis with Cervus and Cucumis Polypeptide Injection (鹿瓜多肽注射液) and to predict its mechanism by network analysis. Methods The information of 4050 patients with osteoarthritis treated with Cervus and Cucumis Polypeptide injection from the HIS database was retrieved, and SAS9.2 and R software were used to conduct frequency and rate statistics on their population characteristics and medication; By analyzing the outcomes of patients with osteoarthritis who used Cervus and Cucumis Polypeptide Injection to judge its effectiveness, and compared with the treatment outcomes of osteoarthritis patients who did not use the Cervus and Cucumis Polypeptide Injection; Clementine 12.0 was used to analyze the combined drugs were analyzed by association rules and sorted by confidence. Utilized CNKI, TCMSP database and Cytoscape software to construct "disease-drug-ingredient-target" network and protein-protein interaction network, and performed topological analysis to screen core ingredients and core targets; Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis was performed; Finally, performed molecular docking between the core ingredients and the core targets. Results Among the 4050 patients with osteoarthritis, the age group of 46-65 years was the most (2248 cases, 55.51%), followed by 66-75 years old (850 cases, 20.99%), among which female patients accounted for the majority(2657, 70.35%). The total effective rate of 4050 osteoarthritis patients treated with Cervus and Cucumis Polypeptide Injection was 97.88%, and the comparison of osteoarthritis patients with and without Cervus and Cucumis Polypeptide Injection showed that the efficacy of Cervus and Cucumis Polypeptide Injection was more effective. Association rules showed that the common concomitant drugs of Cervus and Cucumis Polypeptide Injection in the treatment of osteoarthritis are hormones (betamethasone), antibiotics (cefazolin), anti-inflammatory and analgesic (bone peptide injection), and traditional Chinese medicine to tonify kidney and strengthen bones (Jintiange Capsules), promote blood circulation and remove stasis (Maixuekang Capsule). Target-network analysis obtained 10 core ingredients including palmitic acid, myristic acid, tryptophan, vitamin A, etc; Nine core targets including:peroxisome proliferator-activated receptor gamma (PPARG), myeloperoxidase (MPO), receptor-type tyrosine-protein phosphatase C (PTPRC), etc, among which the combination with better molecular docking were:vitamin A and mitogen-activated protein kinase 14 (MAPK14), tryptophan and matrix metalloproteinase 9 (MMP9), vitamin A and PTPRC. The results of GO and KEGG analysis mainly involved:immune inflammation, hormone secretion, blood circulation and MAPK pathway. Conclusion The patients with osteoarthritis treated by Cervus and Cucumis Polypeptide Injection are mainly female middle-aged and elderly people, and the common syndromes are liver and kidney deficiency, damp-heat, qi stagnation and blood stasis syndrome; Chinese medicine treatment is mostly combined with kidney-tonifying and bone-strengthening, blood circulation-promoting and stasis-removing drugs to treat both the incidental and fundamental aspects, and Western medicine treatment often concentrate in relieving symptoms. However, through target-network research, it was concluded that Cervus and Cucumis Polypeptide Injection mainly play a role in the regulation of MMP9, MPO and other targets through vitamin A and amino acids. This conclusion can provide reference for further research and clinical application.

R285.64

国家重点研发计划项目（2018YFC1707400）；2018重点研发计划：中医“治未病”服务技术体系的构建（2018YFC1704705）；2021年岐黄学者支持项目