This study aimed to detect the combined effects of gallic acid (GA)and ciprofloxacin (CIP)on the murine chronic rhinosinusitis(CRS)model in mice.Pseudomonas aeruginosa from refractory CRS nasal samples were isolated and a CRS model in mice was induced.GA and CIP were intragastrically administered singly or in combination.The nasal histopathologic change was observed by hematoxylin and eosin (HE)staining.The concentration of TNF-α;IL-6 and IL-8 in serum were determined by ELISA assay.The activity of SOD and contents of MDA and ROS were measured with commercially available kits.The expressions of IκB;NF-κB p65;TNF-α;IL-6 and IL-8 in nasal mucosa tissues were measured by Western blotting assay.The results showed that the inflammation of CRS in each treatment group was significantly attenuated.The expression level of TNF-α;IL-6;IL-8;MDA;NF-κB p65 and the contents of ROS were reduced significantly in treated groups;while the activity of SOD and the expression level of IκB were increased.More obvious effects were achieved in CA and CIP combined group.The data showed that combination of GA and CIP was superior to GA or CIP alone;and the combined therapy might be related with inhibiting NF-κB signaling pathway and downregulating the expressions of TNF-α;IL-6 and IL-8.

Objective: To observe the effect of tumor necrosis factor-α (TNF-α) monoclonal antibody on autophagy in allergic rhinitis (AR) mice. Methods: Thirty six weeks old BALB/c mice were randomly divided by random number table method into five groups: control group, model group (AR group), TNF-α antibody intervention group (AR+TNF-α group), autophagy inhibitor (3-methylindole, 3-NA) intervention group (AR+3-MA group), TNF-α antibody combined with autophagy inducer rapamycin (RAP) intervention group (AR+TNF-α+RAP group), with 6 mice in each group. AR model was established by conventional method, the corresponding reagent was administered before nasal cavity stimulation sensitization and during the whole experiment. Behavioral scores of mice were obtained, blood was collected from the eye socket, and mice in each group were sacrificed to collect nasal mucosa tissue samples. Pathological changes of nasal mucosa were observed by hematoxylin-eosin staining. Expression levels of inflammatory factor and IgE in serum were detected by enzyme-linked immunosorbent assay (ELISA). Expressions of autophagy related indicators microtubule-associated protein-1 light chain-3B (LC3B), Beclin-1, sequestosome1 (p62), autophagy-related 5 (ATG5), autophagy-related 7 (ATG7) were measured by Real-time PCR and Western blot. The aggregation of LC3B protein was observed by immunofluorescence. SPSS 19.0 software was used for statistical analysis. Results: Compared with the AR model group, symptoms of AR in AR+TNF-α group and AR+3-MA group were mild; the pathological changes of nasal mucosa were weak; the expression of IgE, TNF-α, interleukin 4 (IL-4), interferon-γ (IFN-γ) in serum significantly reduced (IgE: 666.19±78.35 (±s) vs. 692.38±64.29 vs. 1 059.05±146.44, TNF-α: 112.06±12.95 vs. 113.17±15.43 vs. 161.22±17.96, IL-4: 54.05±7.14 vs. 58.26±5.67 vs. 79.95±6.33, IFN-γ: 28.58±4.51 vs. 30.67±2.60 vs. 39.83±3.31, all P<0.05), and the expression of LC3B Ⅱ/Ⅰ, Beclin-1, ATG5, ATG7 in nasal mucosa significantly decreased, the expression of p62 significantly elevated. After intervention with autophagy inducer RAP, the therapeutic effect of TNF-α monoclonal antibodies on AR was antagonized. Conclusion TNF-α monoclonal antibody significantly improves nasal symptoms in AR mice by inhibiting autophagy levels.