中药药理与临床2025，Vol.41Issue(10)：37-45,9.
毒素清抑制EGFR/ERK保护肺泡上皮屏障改善衰老小鼠肺炎模型
Dusuqing Protects the Alveolar Epithelial Barrier to Ameliorate Pneumonia in Aging Mice by Inhibiting EGFR/ERK Signaling
摘要
Abstract
Objective:To investigate the mechanism of Dusuqing(毒素清)in protecting the alveolar epithelial barrier and ameliorating pneumonia in aging mice.Methods:Seventy-two SPF-grade C57BL/6J mice were used in this study,from which 36 mice were randomly selected and in-jected subcutaneously with D-galactose(200 mg/kg)at the back of the neck for the modeling of aging,and the remaining mice(youth group)were injected with normal saline once daily for 8 weeks.Thirty aging mice and 30 youth mice were respectively randomized into blank control,model control,Dusuqing(15.6 g/kg and 7.8 g/kg),and ceftriaxone sodium groups.One-time intratracheal dripping of Klebsiella pneumoniae was performed for the modeling of pneumonia.After 6 h,mice were administrated with corresponding drugs or normal saline by gavage and then were euthanized on day 3.The organ wet mass/body weight index was determined to calculate the organ index.Oxidative stress was measured by biochemical test kits.Pathological changes in the lung tissue were observed through hematoxylin-eosin staining.The levels of in-flammatory factors were determined by enzyme-linked immunosorbent assay.The expression of zona occludens-1(ZO-1)and occludin(OCC)was detected by Western blotting and immunofluorescence assay.Additionally,the expression levels of cyclin-dependent kinase inhib-itor 1A(P21),myeloperoxidase(MPO),neutrophil elastase(NE),phosphorylated epidermal growth factor receptor(p-EGFR),and phos-phorylated extracellular signal-regulated kinase(p-ERK)were analyzed by immunohistochemistry.Results:Compared with the youth group,the aging group showed decreases in spleen index,thymus index,and superoxide dismutase(SOD)content(P<0.05 or P<0.01)and increa-ses the malondialdehyde(MDA)and P21 levels(P<0.01).Compared with the blank control group,the model control group presented in-flammatory cell infiltration,lung interstitial and intra-alveolar edema,thickened lung septa,and increased lung injury and alveolitis scores(P<0.01).Compared with the model control group,Dusuqing(7.8 g/kg and 15.6 g/kg)and ceftriaxone sodium groups showed clear alveolar structures,reduced inflammatory cell infiltration,and decreased lung injury and alveolitis scores(P<0.05 or P<0.01).Compared with the youth model control group,the aging model control group exhibited severe inflammatory cell infiltration.Compared with the youth Dusuqing(15.6 g/kg)group,the aging Dusuqing(15.6 g/kg)group showed reduced inflammatory cell infiltration and declined lung injury and alve-olitis scores.Compared with the aging blank control group,the aging model control group showed increases in total cell count and expression levels of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),MPO,and NE but decreases in the expression levels of ZO-1 and OCC in the bronchoalveolar lavage fluid(P<0.05 or P<0.01).Compared with the aging model control group,the aging Dusuqing(15.6 g/kg)group presented declines in alveolitis score,lung injury score,total cell count,and expression levels of IL-6,TNF-α,MPO,and NE(P<0.05 or P<0.01)but upregulation in the expression levels of ZO-1 and OCC(P<0.05 or P<0.01).Network pharmacology enrichment of 333 core targets of Dusuqing indicated that the amelioration of pneumonia in aging mice by Dusuqing may be associated with EGFR,ERK,and MAPK signaling pathways.Specifically,EGFR showed good binding affinity with both sinoacutine and isoliquiritigenin.Dusuqing at 15.6 g/kg down-regulated the expression levels of p-EGFR and p-ERK in the lung tissue of the mouse model of pneumonia-aging(P<0.05 or P<0.01).Conclusion:Dusuqing protects the alveolar epithelial barrier and ameliorates pneumonia in aging mice by inhibiting EGFR/ERK signaling.关键词
毒素清/衰老小鼠肺炎模型/肺泡上皮屏障/表皮生长因子受体/细胞外信号调节激酶Key words
Dusuqing/Mouse model of pneumonia-aging/Alveolar epithelial barrier/Epidermal growth factor receptor(EGFR)/extracellular signal-regulated kinase(ERK)引用本文复制引用
万冉,程俞梦,程思远,江宇航,赵帅军,赵鹏,刘学芳..毒素清抑制EGFR/ERK保护肺泡上皮屏障改善衰老小鼠肺炎模型[J].中药药理与临床,2025,41(10):37-45,9.基金项目
河南省高等学校重点科研项目(编号:24A360013) （编号:24A360013）
河南省本科高校青年骨干教师培养计划(编号:2023GGJS084) （编号:2023GGJS084）
河南省高校科技创新人才支持计划(编号:24HASTIT073). （编号:24HASTIT073）
