世界科学技术-中医药现代化2024,Vol.26Issue(11) :2937-2950.DOI:10.11842/wst.20240102002

基于网络药理学探讨脏痹方治疗TNF-Tg小鼠类风湿关节炎并发心肌肥厚的疗效研究

Study on the Efficacy of Zang Bi Formula in Treatment Rheumatoid Arthritis and its Cardiac Hypertrophy Complications in TNF-Tg Mice Based on Network Pharmacology

周茂琳 王怿 李雪菲 杨灿 马梦娇 阮铭 王杰 徐浩 施杞 王佑华 梁倩倩
世界科学技术-中医药现代化2024,Vol.26Issue(11) :2937-2950.DOI:10.11842/wst.20240102002

基于网络药理学探讨脏痹方治疗TNF-Tg小鼠类风湿关节炎并发心肌肥厚的疗效研究

Study on the Efficacy of Zang Bi Formula in Treatment Rheumatoid Arthritis and its Cardiac Hypertrophy Complications in TNF-Tg Mice Based on Network Pharmacology

周茂琳 1王怿 1李雪菲 2杨灿 2马梦娇 1阮铭 2王杰 2徐浩 2施杞 2王佑华 1梁倩倩2
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作者信息

  • 1. 上海中医药大学附属龙华医院 上海 200032
  • 2. 上海中医药大学附属龙华医院 上海 200032;上海中医药大学脊柱病研究所 上海 200032;筋骨理论与治法教育部重点实验室 上海 200032
  • 折叠

摘要

目的 通过动物实验观察脏痹方(ZBF)在类风湿关节炎(RA)心脏并发症中的疗效.采用超高效液相色谱串联飞行时间质谱(UHPLC-TOF-MS)和网络药理学分析ZBF治疗心肌肥厚的活性成分、靶点、通路,运用分子对接验证成分与通路相关蛋白的结合能力.方法 采用TNF转基因(TNF-Tg)小鼠作为RA及其心肌肥厚并发症模型,ZBF连续灌胃8周后通过超声心动图观察小鼠左心室肥厚情况,WGA染色、HE染色、Masson染色用于观察分析心脏组织的病理变化.采用UHPLC-TOF-MS技术鉴定ZBF的化学成分.利用公共数据库筛选活性成分及成分靶点、疾病靶点,构建互作网络,并进行生物富集分析以及活性成分与蛋白的对接能力分析.结果 动物实验中,ZBF降低了 TNF-Tg小鼠的心重指数、心重胫骨长比(P<0.05,P<0.01),减轻了心肌肥厚(P<0.001)和心肌细胞的肥大(P<0.01),缓解了心脏的炎症浸润和纤维化(P<0.0001).通过UHPLC-TOF-MS共从ZBF中鉴定出24个化合物.通过网络药理学分析共筛选出105种ZBF的活性成分,构建了 ZBF治疗心肌肥厚187个潜在靶点,富集通路中具有意义的有PI3K-AKT信号通路、TNF信号通路、MAPK信号通路.结论 ZBF减轻了 TNF-Tg小鼠的心肌肥厚和心肌细胞的肥大,缓解了心脏的炎症浸润和纤维化,ZBF或可成为临床中治疗RA及其心脏并发症的潜在药物.

Abstract

Objective The efficacy of Zang Bi Formula(ZBF)in cardiac complications of rheumatoid arthritis(RA)was observed through animal experiments.Ultra-high performance liquid chromatography tandem time-of-flight mass spectrometry(UHPLC-TOF-MS)and network pharmacology was used to analyze the active ingredients,targets,and pathways of ZBF for the treatment of cardiac hypertrophy,and molecular docking was applied to verify the binding ability of the ingredients to pathway-related proteins.Methods TNF transgenic(TNF-Tg)mice were used as RA and RA-complexed cardiac hypertrophy models,and the left ventricular hypertrophy of mice was observed by echocardiography after 8 weeks of continuous gavage with ZBF,and WGA staining,HE staining,and Masson staining were used to observe and analyze the pathological changes of cardiac tissues.The chemical composition of ZBF was identified by UHPLC-TOF-MS technique.The public database was then used to screen the active ingredients and component targets and disease targets,construct interaction networks,and analyze the bioconcentration data as well as the docking ability of the active ingredients and proteins.Results In animal experiments,ZBF reduced cardiac weight index and cardiac weight tibia length ratio in TNF-Tg mice(P<0.05,P<0.01),attenuated cardiac hypertrophy(P<0.001)and cardiomyocyte hypertrophy(P<0.01),and alleviated inflammatory infiltration and fibrosis in the heart(P<0.0001).A total of 24 compounds were identified from ZBF by UHPLC-TOF-MS.A total of 105 active ingredients of ZBF were screened by network pharmacological analysis,and 187 potential targets of ZBF for cardiac hypertrophy were constructed,and the enriched pathways with significance included PI3K-AKT signaling pathway,TNF signaling pathway,and MAPK signaling pathway.Conclusion ZBF attenuated myocardial hypertrophy and cardiomyocyte hypertrophy in TNF-Tg mice and alleviated inflammatory infiltration and fibrosis in the heart,and ZBF may be a potential drug for the treatment of RA and its cardiac complications in the clinic.

关键词

类风湿关节炎心脏并发症/心肌肥厚/脏痹方/TNF-Tg小鼠

Key words

Rheumatoid arthritis cardiac complications/Cardiac hypertrophy/Zang Bi Formula(ZBF)/TNF transgenic(TNF-Tg)mice

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出版年

2024
世界科学技术-中医药现代化
中科院科技政策与管理科学研究所,中国高技术产业发展促进会

世界科学技术-中医药现代化

CSTPCD北大核心
影响因子:1.175
ISSN:1674-3849
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