重组人干扰素γ对变应性鼻炎大鼠Toll样受体4/核因子-B信号通路及血清炎症因子的影响

Effect of recombinant human interferon gamma on TLR4/NF-B signaling pathway and serum inflammatory factors in allergic rhinitis rats

目的分析重组人干扰素γ对变应性鼻炎大鼠Toll样受体(TLR4)/核因子-B(NF-B)信号通路及血清炎症因子影响。方法选取SPF级Wistar雄性大鼠60只,随机数字表法将大鼠分为正常组、模型组与实验组,模型组与实验组制备AR模型,由第22天建立模型后,依据人和动物剂量转换公式,实验组大鼠采用20 IU的重组人干扰素γ(IFN-γ)滴鼻治疗,1次/天,正常组与模型组采用等剂量生理盐水滴鼻,持续14 d。观察各组大鼠行为学评分、鼻黏膜病理形态、血清炎症因子含量及鼻黏膜组织TLR4、NF-B p65蛋白与mRNA表达情况。结果强化致敏7 d完成后,实验组大鼠行为学评分为(7.68±1.52)分,模型组为(7.81±1.43)分,均高于正常组的(2.95±0.57)分,差异有统计学意义(t=13.031、14.119,P=0.001、0.001);末次给药后实验组大鼠流涕、喷嚏和挠鼻等状况较模型组显著好转,行为学评分降低至(3.98±0.64)分,较模型组的(8.49±1.53)分差异有统计学意义(t=12.161,P=0.001)。模型组大鼠鼻黏膜内肥大细胞、嗜酸粒细胞数量较正常组升高,实验组大鼠鼻黏膜内肥大细胞、嗜酸粒细胞数量较模型组降低,差异有统计学意义(P<0.05)。模型组大鼠血清IFN-γ、白细胞介素-10(IL-10)含量低于正常组,免疫球蛋白E(IgE)、肿瘤坏死因子-α(TNF-α)、白细胞介素-4(IL-4)、白细胞介素-6(IL-6)含量高于正常组;实验组大鼠血清IFN-γ、IL-10含量高于模型组,IgE、TNF-α、IL-4、IL-6含量低于模型组,差异有统计学意义(P<0.05)。模型组大鼠鼻黏膜组织TLR4、NF-B p65蛋白与mRNA表达较正常组升高,实验组大鼠鼻黏膜组织TLR4、NF-B p65蛋白与mRNA表达较模型组降低,差异有统计学意义(P<0.05)。结论重组人干扰素γ可降低变应性鼻炎大鼠血清炎症因子含量,减少生成IgE,调节T细胞免疫失衡,其作用机制可能和抑制TLR4/NF-B信号通路表达有关。

Objective To analyze the effect of recombinant human interferonγon TLR4/NF-B signaling pathway and serum in‐flammatory factors in allergic rhinitis(AR)rats.Methods Sixty SPF Wistar male rats were selected and divided into normal group,model group and experimental group by random number table method.AR models were prepared in the model group and experimental group.On the 22nd day after model establishment,according to the human and animal dose conversion formula,rats in the experimen‐tal group were treated with 20 IU of recombinant human IFN-γnasal drops intranasally once a day,and the normal group and the model group received nasal drops of normal saline for 14 days.The behavioral scores,pathological morphology of nasal mucosa,the content of serum inflammatory factors and the expression of TLR4,NF-B p65 protein and mRNA in nasal mucosa of each group of rats were ob‐served.Results After 7 days of intensive sensitization,the behavioral score of rats was(7.68±1.52)points in the experimental group and(7.81±1.43)points in the model group,which were higher than that in the the normal group(2.95±0.57)points.The differences were statistically significant(t=13.031,14.119,P=0.001,0.001);after the last administration,the conditions of runny nose,sneezing,and scratching the nose in the experimental group were significantly improved compared with the model group,and the behavioral score was reduced to(3.98±0.64)points.Compared with the model group(8.49±1.53),the difference was statistically significant(t=12.161,P=0.001).The number of mast cells and eosinophils in the nasal mucosa of the model group rats was higher than that in the normal group,while the number of mast cells and eosinophils in the nasal mucosa of the experimental group rats was lower than that in the model group.The difference was statistically significant(P<0.05).The levels of serum IFN-γand IL-10 in the model group were lower than those in the normal group,and the contents of IgE,TNF-α,IL-4,and IL-6 were higher than those in the normal group;Compared with the model group,the contents of IgE,TNF-α,IL-4 and IL-6 were lower than the model group,and the difference was statistically significant(P<0.05).The expressions of TLR4,NF-B p65 protein and mRNA in the nasal mucosa of the model group rats were higher than those in the normal group,while the expressions of TLR4,NF-B p65 protein and mRNA in the nasal mucosa of the model group rats were lower than those in the model group,and the differences were statistically significant(P<0.05).Conclusion Recombinant hu‐man interferonγcan reduce serum inflammatory factor content,reduce IgE production,and regulate T cell immune imbalance in rats with allergic rhinitis.The mechanism may be related to the inhibition of TLR4/NF-B signaling pathway expression.