基于网络药理学和动物实验探讨益肺解毒颗粒对急性肺损伤小鼠炎症反应及免疫功能的影响  

Protective effects of Yifei Jiedu granules on inflammatory response and immune functionwith acute lung injury in mice based on network pharmacology and animal experiments

作　　者：王园 杨允 王博[2] 马战平 杨栓柱 刘洋[1] 龙凯花 王海峰 WANG Yuan;YANG Yun;WANG Bo;MA Zhanping;YANG Shuanzhu;LIU Yang;LONG Kaihua;WANG Haifeng(Shaanxi Academy of Traditional Chinese Medicine,Xi’an 710003,China)

机构地区：[1]陕西省中医药研究院,陕西西安710003 [2]西北大学,陕西西安710069 [3]陕西省中医医院,陕西西安710003 [4]武警陕西省总队医院,陕西西安710054

出　　处：《陕西中医》2024年第12期1619-1624,共6页Shaanxi Journal of Traditional Chinese Medicine

基　　金：陕西省重点研发计划项目(2022ZDXM-SF-06,2024SF-YBXM-489);国家中医药管理局科技司科研项目;陕西省中医药管理局新冠专项(ZYJXG-L23002);陕西省科协青年人才托举计划项目(20230321);西安市科技计划项目(23YXYJ0142)。

摘　　要：目的:通过网络药理学和动物实验探讨益肺解毒颗粒对脂多糖(LPS)所致急性肺损伤(ALI)小鼠的影响及保护作用。方法:利用Swiss Target Prediction等平台,对药物的靶点进行筛选;利用Gene Cards数据库以“acute lung injury”为关键词整理疾病靶点;利用STRING平台进行蛋白互作分析,Cytoscape 3.7.2可视化交集靶点网络图并对核心靶点筛选;微生信平台进行KEGG通路富集和GO分析,Cytoscape 3.7.2构建成分-靶点-通路网络图。将30只C57小鼠随机分为空白组、模型组和低、中、高剂量组,模型及给药组采用LPS气管内滴注的方法建立ALI模型。记录小鼠体重变化;测定胸腺与脾脏指数;测定血清和肺泡灌洗液(BALF)中白介素-6(IL-6)、白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)的含量;HE染色法观察肺组织病理变化。结果:筛选后获得药物靶点277个,成分与疾病的交集靶点146个,关键靶点有CASP3、EGFR、ESR1等,GO功能结果共1766个,KEGG富集结果有178条通路,PI3K-Akt信号通路为关键通路。相较空白组,模型组的胸腺与脾脏指数显著下降(均P<0.05);血清与BALF中IL-6、IL-1β、TNF-α含量显著增加(均P<0.05);肺组织明显出现炎性细胞浸润和出血。与模型组相比,给药组的胸腺指数显著增加(均P<0.05);高剂量组血清和BALF中炎症因子含量显著降低(均P<0.05)。结论:益肺解毒颗粒能改善因LPS所致的ALI小鼠肺组织病理损伤,其机制可能与增强免疫功能和抑制炎症因子分泌有关。Objective:To investigate the protective effects of Yifei Jiedu granules lipopolysaccharide-induced acute lung injury in mice based on network pharmacology and animal experiments.Methods:Using Swiss Target Prediction platformetc,drug targets were screened.Using Gene Cards database and using“acute lung injury”as the key words to collate disease targets.The STRING platform was used for protein interaction analysis,and Cytoscape 3.7.2 software was used to visualize the intersection target network diagram and screen the core targets.Weishengxin platform were used for KEGG pathway enrichment and GO analysis.The components-targets-pathways network diagram is constructed using Cytoscape 3.7.2.Thirty male C57 mice were randomly divided into the blank group,the model group,and the Yifei Jiedu granules low,medium,high-dose groups,the model of acute lung injury was established by endotracheal infusion of LPS in the model group,and the Yifei Jiedu granules low,medium,high-dose groups.The weight of mice,thymus index and spleen index were analyzed.The levels of IL-6,IL-1β,TNF-αin serum and bronchoalveolar lavage fluid were determined.HE staining was used to observe the lung tissues histopathological changes.Results:After screening,277 gene targets of Yifei Jiedu granules were obtained,there were 146 intersection targets between components and disease,among which the key targets included CASP3,EGFR,ESR1 etc.There were 1766 results in GO function,178 mechanism pathways were obtained by KEGG enrichment analysis.The PI3K-Akt signal pathway is the key pathway.Compared with the blank group,the thymus index and spleen index in the model group were decreased(P<0.05),the levels of three inflammatory cytokine in serum and BALF were increased(P<0.05),the lung tissue with inflammatory cell infiltration and bleeding.Compared with the model group,the thymus index in medication administration groups was increased(all P<0.05),the levels of inflammatory cytokine in Yifei Jiedu granules high-dose group in serum and BALF were decreased(P<0.

关 键 词：急性肺损伤 益肺解毒颗粒 网络药理学 脂多糖 炎症因子 免疫功能 

分 类 号：R563[医药卫生—呼吸系统]