中国病理生理杂志2026,Vol.42Issue(8):1579-1590,12.DOI:10.3969/j.issn.1000-4718.2026.08.011
补肺健脾方通过抑制MAPK信号通路减轻COPD大鼠结肠损伤
Bufei-Jianpi formula alleviates colonic injury in COPD rats by inhibiting MAPK signaling pathway
摘要
Abstract
AIM:To investigate the effect and mechanism of Bufei-Jianpi formula(BJF)on colonic injury in rats with chronic obstructive pulmonary disease(COPD).METHODS:Sprague-Dawley(SD)rats were randomly divid-ed into five groups(n=6 per group):control group,model group,low-dose BJF group(6.21 g/kg),high-dose BJF group(12.42 g/kg),and doxofylline(DOX,36 mg/kg)group.Rats in the control group were exposed to fresh air,whereas those in the other groups were exposed to cigarette smoke for eight consecutive weeks combined with intranasal instillation of Klebsiella pneumoniae to establish a COPD rat model.After model establishment,rats were administered 0.5%sodium carboxymethyl cellulose solvent,different doses of BJF,or doxofylline for eight weeks.Subsequently,body weight was measured.Pulmonary function was assessed by tidal volume(TV),minute ventilation(MV),peak expiratory flow(PEF),and expiratory flow at 50%of tidal volume(EF50).Morphological alterations in lung and colonic tissues were ob-served via hematoxylin-eosin(HE)staining.Pulmonary histopathological damage was assessed using mean alveolar num-ber(MAN)and mean linear intercept(MLI),while colonic histopathological damage was evaluated by pathological injury scores.The expression levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 in lung and co-lon tissues were measured using ELISA.In a separate experiment,12 SD rats were randomly divided into two groups(n=6 per group):a control group and a BJF group,which received saline or BJF,respectively.Blood samples were collected,and serum was isolated.High-performance liquid chromatography-mass spectrometry(HPLC-MS)was performed to identi-fy the absorbed components of BJF in the blood,and network pharmacology was used to screen the core components,key targets,and potential pathways.Molecular docking and immunohistochemistry were further employed to validate the pre-dicted mechanisms.RESULTS:Low-or high-dose BJF significantly improved body weight(P<0.01)and pulmonary function parameters(TV,MV,PEF,and EF50)(P<0.01),reduced alveolar structural damage and inflammatory cell in-filtration in lung tissue,and significantly improved MAN and MLI(P<0.01).Low-or high-dose BJF also significantly im-proved the scores of colonic pathological injury(P<0.05,P<0.01)and decreased the levels of TNF-α,IL-1β,and IL-6 in both lung and colonic tissues(P<0.01).Component identification and network pharmacology analysis indicated that ten core components of BJF absorbed into the blood,including magnolol and astragalin,may regulate signaling pathways such as the mitogen-activated protein kinase(MAPK)pathway and the phosphatidylinositol 3-kinase/protein kinase B(PI3K-Akt)pathway by acting on key targets including TNF,AKT serine/threonine kinase 1(AKT1),and IL-1β.Molec-ular docking confirmed strong binding affinities between the core components and core targets.Immunohistochemical anal-ysis of three core proteins in the MAPK pathway in colonic tissues revealed that BJF significantly inhibited the expression of p-p38,p-ERK,and p-JNK(P<0.01).CONCLUSION:BJF alleviates colonic pathological injury and the inflammato-ry response in COPD rats,possibly by inhibiting the MAPK signaling pathway.关键词
补肺健脾方/慢性阻塞性肺疾病/结肠病变/网络药理学/分子对接/MAPK信号通路Key words
Bufei-Jianpi formula/chronic obstructive pulmonary disease/colonic lesion/network pharmacol-ogy/molecular docking/MAPK signaling pathway分类
医药卫生引用本文复制引用
刘览,陶柳颖,赵鹏,任周新..补肺健脾方通过抑制MAPK信号通路减轻COPD大鼠结肠损伤[J].中国病理生理杂志,2026,42(8):1579-1590,12.基金项目
河南省高等学校重点科研项目(No.24A360013) (No.24A360013)