紫锥菊多糖对克雷伯菌诱导的肺炎模型大鼠肺部炎症损伤机制的影响OA

Objective:To investigate the effect of echinacea polysaccharide on pulmonary inflammation injury in a Klebsiella pneumoniae-induced pneumonia rat model and explore its anti-inflammatory mechanism.Methods:A pneumo-nia rat model was established using Klebsiella pneumoniae and divided into five groups:model control group,echinacea polysaccharide 5 mg/kg group,echinacea polysaccharide 10 mg/kg group,Toll-like receptor 4(TLR4)activator 25 μg/kg group,and echinacea polysaccharide 10 mg/kg+TLR4 activator 25 μg/kg group,with 20 rats in each group.Each group received corresponding interventions for 14 days.Lung function parameters(lung capacity,lung resistance,and lung compliance)were detected by an animal lung function analyzer.The levels of TLR4,T cell immunoglobulin mucin molecule-3(TIM-3),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in bronchoalveolar lavage fluid(BALF)were detected by enzyme-linked immunosorbent assay(ELISA).Bacterial counts in BALF were determined by traditional culture methods.White blood cell(WBC)and polymorphonuclear neutrophil(PMN)counts in BALF were determined by an automated hematology analyzer and a microscope,respectively.Pathological injury of lung tissue was observed by hematoxylin-eosin staining.Immunohistochemistry was used to detect CD11-positive expression,a marker of M1 macrophage polarization.Western blotting was employed to detect the expression of CD11,CD206(M2 macrophage marker),T-box transcription factor(T-BET),GATA binding protein 3(GATA3),fimbrial adhesion protein(FIMH),TLR4,phosphorylated NF-κB(p-NF-κB),total NF-κB,and TIM-3 in lung tissue.Results:Compared with the normal control group,the model control group showed alveolar wall congestion,significant infiltration of inflammatory cells around the bronchi,and extensive areas of lesions.Lung capacity,lung compliance,and the expression of CD206 and GATA3 in lung tissue were significantly decreased,while lung resistance,levels of TLR4,TIM-3,TNF-α,IL-6,bacterial count,WBC,and PMN in BALF,and the expression of CD11-positive cells,CD11,T-BET,FIMH,TLR4,p-NF-κB/NF-κB,and TIM-3 proteins were significantly increased(P<0.01).Compared with the model control group,pathological damage,in-cluding alveolar injury and inflammatory infiltration in the echinacea polysaccharide 5 mg/kg and 10 mg/kg groups was alleviated to varying degrees.Lung capacity,lung compliance,and the expression of CD206 and GATA3 in lung tissue were increased in a dose-dependent manner,while lung resistance,BALF levels of TLR4,TIM-3,TNF-α,IL-6,bacterial count,WBC,PMN,and expression of CD11-positive cells,CD11,T-BET,FIMH,TLR4,p-NF-κB/NF-κB,and TIM-3 were decreased successively(P<0.01).Rats in the TLR4 activator group exhibited severe alveolar rupture,the most extensive inflammatory infiltration,and the largest areas of lesions,with significantly decreased lung capacity,compliance,CD206,and GATA3 expression,and significantly increased indicators of inflammation(P<0.01).In the echinacea polysaccha-ride 10 mg/kg+TLR4 activator 25 μg/kg group,pathological changes and inflammatory markers worsened compared to the echinacea polysaccharide 10 mg/kg group but were improved relative to the TLR4 activator 25 μg/kg group alone(P<0.01).Conclusions:Echinacea polysaccharide may improve lung function in the Klebsiella pneumoniae-induced pneumonia model rats by inhibiting the TLR4/NF-κB pathway,enhancing anti-inflammatory immune cell activation,and relieving lung inflammation and pathological damage.