番茄红素对金黄色葡萄球菌诱导小鼠乳腺炎的多维度抑制效应分析OA

This study aimed to investigate the protective effects and underlying mechanisms of lycopene(LYC)on Staphylococcus aureus(S.aureus)-induced mastitis in mice.A total of 36 pregnant Kunming mice(6-8 weeks old)were randomly divided into six groups:Control,LYC,Model,Low-dose,Medium-dose,and High-dose groups.From mid-pregnancy(day 7 after vaginal plug detection),the LYC,Low-,Medium-,and High-dose groups were administered 50,12.5,25,and 50 mg/(kg·bw)of LYC by gavage once daily,respectively,while the Control and Model groups received an equal volume of corn oil.After 28 days of treatment,mastitis was induced by injecting S.aureus suspension(2×10⁸ CFU/mL)into the mammary ducts(Control group and LYC group received no treatment).After 24 hours,the mice were euthanized,and the anatomical changes in the mammary glands were observed.The fourth pair of mammary glands was collected for histopathological analysis by hematoxylin and eosin(H.E.)staining.Levels of inflammatory cytokines[tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)]were measured using enzyme-linked immunosorbent assay(ELISA),and the expression of tight junction proteins[zonula occludens-1(ZO-1),Occludin,and Claudin-3]was evaluated by Western blot(WB).Additionally,the antibacterial activity of LYC against S.aureus was determined using the broth microdilution method to measure its minimum inhibitory concentration(MIC)and growth curve.Hemolytic assays and WB were used to assess S.aureus hemolytic activity and α-hemolysin(Hla)expression,respectively.The results showed that compared with the Control group,the Model group exhibited mammary tissue hemorrhage,destruction and thickening of alveolar wall structure,infiltration of inflammatory cells,a significantly higher tissue injury score(P<0.01),significantly elevated levels of TNF-α,IL-1β,and IL-6(P<0.01),and significantly decreased expression of ZO-1,Occludin,and Claudin-3(P<0.01).These pathological changes were significantly reversed by LYC treatment in all dose groups(P<0.05 or P<0.01).No significant differences were observed between the Control group and the LYC group across all indicators(P>0.05).The MIC of LYC against S.aureus was 128 μg/mL.Sub-inhibitory concentrations of LYC(16,32,and 64 μg/mL)significantly suppressed hemolytic activity(P<0.01)and dose-dependently reduced Hla expression(P<0.01),whereas 8 μg/mL LYC had no significant effect(P>0.05).In conclusion,LYC alleviates S.aureus-induced mastitis by modulating host inflammatory responses and bacterial virulence,providing a novel strategy for the prevention and control of mastitis through natural products targeting host-pathogen interactions.