中国病理生理杂志2025，Vol.41Issue(3)：524-533,10.DOI:10.3969/j.issn.1000-4718.2025.03.013
清肺解毒化痰方对重症肺炎小鼠肺血管内皮屏障及VEGF/P38通路的影响
Effects of Qingfei-Jiedu-Huatan formula on VEGF/P38 pathway and pul-monary vascular endothelial barrier in mice with severe pneumonia
摘要
Abstract
AIM:To investigate the effects of the Qingfei-Jiedu-Huatan formula(QJHF)on damage to the lung vascular endothelial barrier induced by Klebsiella pneumoniae in mice with severe pneumonia,as well as to elucidate its underlying mechanisms.METHODS:Fifty-one C57BL/6J mice were randomly divided into control group(n=6),model group(n=15),QJHF group(n=15),and ceftriaxone sodium(CRO)group(n=15).Severe pneumonia was in-duced in the mice by a single tracheal intubation with 50 µL of 1×1011 CFU/mL Klebsiella pneumoniae on day 0.Six hours after modeling,the mice in QJHF and CRO groups received their respective treatments,while those in control and model groups were administered an equal volume of saline.All mice were sacrificed on day 3 after the end of gavage.Lung histo-pathological changes were assessed using hematoxylin-eosin(HE)staining.Levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in lung tissues were measured by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to detect CD11b+Ly6g+cells in bronchoalveolar lavage fluid(BALF).Proteomics and network pharma-cology analyses were conducted to elucidate the mechanisms of drug action.Western blot was conducted to assess the ex-pression levels of vascular endothelial cadherin(VE-cadherin),zonula occludens-1(ZO-1),occludin,vascular endothe-lial growth factor(VEGF),P38 mitogen-activated protein kinase(P38),and phosphorylated P38(p-P38)in lung tis-sues.RESULTS:Treatment with QJHF significantly attenuated the symptoms such as mental status and respiratory dis-tress,reduced mortality,mitigated lung tissue lesions,and decreased levels of IL-6,TNF-α,IL-1β,as well as BALF to-tal protein concentration,total cell count and neutrophil content in a mouse model of severe pneumonia(P＜0.05 or P＜0.01).Additionally,QJHF increased the expression of VE-cadherin,ZO-1 and occludin proteins in lung tissues.Pro-teomic analysis demonstrated that QJHF modulated the expression of 129 proteins in the lung tissues of mice suffering from severe pneumonia.Network pharmacology identified 328 potential targets associated with 14 major bioactive components of QJHF and 1 665 genes related to severe pneumonia,with 125 overlapping genes between the two datasets.The construc-tion of a protein-protein interaction(PPI)network,along with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the regulated proteins and overlapping genes,indicated that QJHF primarily in-fluenced the PI3K-Akt,MAPK and Rap1 signaling pathways,as well as VEGFR.Western blot analysis showed that QJHF significantly inhibited the expression of VEGF and P38 in lung tissues(P＜0.05 or P＜0.01).CONCLUSION:Treatment with QJHF attenuates severe pneumonia in mice,potentially by inhibiting VEGF/P38 signaling to protect the vascular endothelial barrier.关键词
清肺解毒化痰方/重症肺炎/血管内皮屏障/VEGF/P38信号通路Key words
Qingfei-Jiedu-Huatan formula/severe pneumonia/vascular endothelial barrier/VEGF/P38 sig-naling pathway分类
医药卫生引用本文复制引用
程思远,白云苹,程俞梦,万冉,邢小香,赵鹏,李建生..清肺解毒化痰方对重症肺炎小鼠肺血管内皮屏障及VEGF/P38通路的影响[J].中国病理生理杂志,2025,41(3):524-533,10.基金项目
国家自然科学基金资助项目(No.81904170) （No.81904170）
河南省"双一流"创建学科中医学科学研究专项(No.HSRP-DF-CTCM-2023-1-06) （No.HSRP-DF-CTCM-2023-1-06）
呼吸疾病中医药防治科技创新团队资助项目(No.HSRP-DFCTCM-T-1) （No.HSRP-DFCTCM-T-1）
2024年度河南省高校科技创新人才支持计划资助项目(No.24HASTIT073) （No.24HASTIT073）
