Network analysis-based strategy to investigate the protective effect of cepharanthine on rat acute respiratory distress syndrome.
Network analysis-based strategy to investigate the protective effect of cepharanthine on rat acute respiratory distress syndrome.
复制标题
DOI：
10.3389/fphar.2022.1054339
复制
发表时间：
2022
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
本研究采用网络分析（Network Analysis，NA）和体内实验相结合的方法，探讨并验证千金藤素（Cepharanthine，CEP）治疗急性呼吸窘迫综合征（Acute Respiratory Distress Syndrome，ARDS）的作用机制。使用SwissTargetPrediction数据库搜索CEP的潜在靶点。应用DisGeNET数据库获得与ARDS相关的致病基因。随后构建并可视化了疾病化合物的共同靶基因的蛋白质-蛋白质相互作用网络。通过Enrichr数据库进行功能富集分析。最后，为了进行体内实验验证，我们建立了油酸诱导的ARDS大鼠模型，主要通过组织学评价和ELISA方法来评价CEP对ARDS的保护作用和对炎症的影响。共发现100个基因是CEP靶基因，而153个基因被发现与ARDS相关。PPI网络用于说明与CEP和ARDS相关的基因的链接和目的，其中包含238个节点和2，333个链接。GO和KEGG分析表明，炎症反应及其相关信号通路与CEP介导的ARDS治疗密切相关。通过网络分析，构建了CEP-基因-通路-ARDS关键网络，包括152个节点（5个靶点和6条通路）和744个连接。体内实验结果表明，CEP可减轻ARDS相关的组织病理学改变和肺水肿，减少中性粒细胞浸润和炎性细胞因子的分泌，同时增加血清ResolvinD 1和ResolvinE 1的含量。因此，这些作用增强了抗炎反应。因此，我们的研究结果表明，CEP可以通过ResolvinE 1和ResolvinD 1信号通路治疗油酸诱导的大鼠ARDS，促进炎症消退，为临床治疗ARDS提供了新的途径。
Combined with Network Analysis (NA) and in vivo experimental methods, we explored and verified the mechanism of Cepharanthine (CEP) involved in the treatment of acute respiratory distress syndrome (ARDS). Potential targets of CEP were searched using the SwissTargetPrediction database. The pathogenic genes related to ARDS were obtained using the DisGeNET database. A protein-protein interaction network of common target genes of disease-compound was subsequently built and visualised. Functional enrichment analysis was performed through the Enrichr database. Finally, for in vivo experimental verification, we established an oleic acid-induced ARDS rat model, mainly through histological evaluation and the ELISA method to evaluate both the protective effect of CEP on ARDS and its effect on inflammation. A total of 100 genes were found to be CEP targeted genes, while 153 genes were found to be associated with ARDS. The PPI network was used to illustrate the link and purpose of the genes associated with CEP and ARDS, which contained 238 nodes and 2,333 links. GO and KEGG analyses indicated that inflammatory response and its related signalling pathways were closely associated with CEP-mediated ARDS treatment. Thus, a key CEP–gene–pathway-ARDS network was constructed through network analysis, including 152 nodes (5 targets and 6 pathways) and 744 links. The results of in vivo experiments showed that CEP could alleviate histopathological changes and pulmonary edema related to ARDS, in addition to reducing neutrophil infiltration and secretion of inflammatory cytokines, whilst increasing serum contents of ResolvinD1 and ResolvinE1. Thus, these effects enhance the anti-inflammatory responses. Thus, our results show that CEP can treat oleic acid-induced ARDS in rats via ResolvinE1 and ResolvinD1 signalling pathways that promote inflammation resolution, providing a new avenue to explore for the clinical treatment of ARDS.
登录
查看更多内容
D-诱导蛋白通过激活PTEN/PI3K/AKT途径来预防大鼠油酸诱导的急性呼吸窘迫综合征。
影响因子：
7.3
作者：
Huang, Jian;Wang, Bingjie;Tao, Shaoyi;Hu, Yuexia;Wang, Ning;Zhang, Qiaoyun;Wang, Chunhui;Chen, Chen;Gao, Bingren;Cheng, Xingdong;Li, Yongnan
通讯作者：
Li, Yongnan
影响因子：
3.1
作者：
van Gemert JP;van den Berk IAH;Nossent EJ;Heunks LMA;Jonkers RE;Vlaar AP;Bonta PI
通讯作者：
Bonta PI
影响因子：
5.6
作者：
Jin D;An X;Zhang Y;Zhao S;Duan L;Duan Y;Lian F;Tong X
通讯作者：
Tong X
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
4.5
作者：
Gao K;Song YP;Song A
通讯作者：
Song A