基于网络药理学和实验验证探讨降糖通脉方治疗糖尿病肺损害的作用机制

来源:用户上传      作者:丁念　郑承红

　　 〔摘要〕 目的 通过网络药理学挖掘降糖通脉方治疗糖尿病肺损害的可能活性成分及靶点，并在动物实验中验证降糖通脉方治疗糖尿病肺损害的作用和机制。方法 应用TCMSP数据库及BATMAN-TCM数据库检索降糖通脉方中的活性成分及靶基因，通过GeneCards数据库筛选得到肺损害的疾病靶点，通过GO生物功能分析、KEGG通路富集和Cytoscape 3.7.2软件构建药物-疾病-活性成分-信通路互作网络图。观察降糖通脉方对糖尿病肺损害大鼠模型肺组织TGF-β1/Smads信号通路上的相关蛋白表达的影响，验证降糖通脉方治疗糖尿病肺损害的作用和机制。结果 降糖通脉方中共得到36个活性分子，作用靶点有109个，其中与糖尿病肺损害相关的作用靶点有95个，核心靶基因Smad2、Smad3、Smad7、Skil相关蛋白通过TGF-β1信号通路、AGE-RAGE信号通路以及TNF信号通路等干预糖尿病肺损害。动物实验表明，与模型组相比，降糖通脉方低、中、高剂量均能改善糖尿病肺损害，减少炎症细胞浸润，降低Smad2/3表达（P<0.01），上调Smad7水平（P<0.05），增加SnoN蛋白表达（P<0.05），减少TGF-β1表达（P<0.05）。结论 降糖通脉方具有“多成分-多靶点”的网络作用效应，其发挥作用的机制可能与调控SnoN蛋白干预TGF-β1/Smads信号通路相关。
　　 〔关键词〕 降糖通脉方;糖尿病肺损害;网络药理学;TGF-β1/Smads信号通路;SnoN蛋白
　　 〔中图分类号〕R285.5 〔文献标志码〕A 〔文章编号〕doi：10.3969/j.issn.1674-070X.2022.07.012
　　Mechanism of Jiangtang Tongmai Recipe in treating diabetic lung damage based on network pharmacology and experimental verification
　　DING Nian1，2， ZHENG Chenghong1，2
　　（1. Hubei University of Chinese Medicine， Wuhan， Hubei 430000， China; 2. Wuhan Hospital of Traditional Chinese Medicine， Wuhan， Hubei 430014， China）
　　〔Abstract〕 Objective To explore the possible active ingredients and targets of Jiangtang Tongmai Recipe in treating diabetic lung injury through network pharmacology， and to verify the effect and mechanism of Jiangtang Tongmai Recipe in treating diabetic lung injury in animal experiments. Methods The active components and target genes of Jiangtang Tongmai Recipe were retrieved through the TCMSP database and BATMAN-TCM database. The disease targets of lung damage were screened from GeneCards database. GO biological function analysis， KEGG pathway enrichment and Cytoscape 3.7.2 software were used to construct the drug-disease-active component-signaling pathway interaction network diagram. The effect of Jiangtang Tongmai Recipe on the expression of TGF-β1/Smads signaling pathway in the lung tissue of diabetic rats with lung damage was observed， and the effect and mechanism of Jiangtang Tongmai Recipe on diabetic lung injury were verified. Results A total of 36 active molecules and 109 active targets were obtained in the Jangtang Tongmai Recipe， including 95 active targets associated with diabetic lung damage. The core target genes Smad2， Smad3， Smad7 and SKIL-related proteins intervene in diabetic lung injury through TGF-β1 signaling pathway， AGE-RAGE signaling pathway and TNF signaling pathway. Animal experiments showed that compared with the model group， the low， middle and high doses of Jiangtang Tongmai Recipe could improve the lung damage of diabetic rats， reduce inflammatory cell infiltration， reduce Smad2/3 expression （P<0.01）， increase Smad7 level （P<0.05）， increase SnoN protein expression （P<0.05） and reduce TGF-β1 expression （P<0.05）. Conclusion Jangtang Tongmai Recipe has a "multi-components and multi-targets" network action effect， which may be related to the regulation of SnoN protein to interfere with TGF-β1/Smads signaling pathway.

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