目的：利用甲苯-2，4-二异氰酸酯（TDI）诱发的变应性鼻炎豚鼠模型，评价重组人白细胞介素-1受体拮抗剂（ rhIL-1ra）的治疗效果。方法以TDI作为致敏剂，通过致敏和激发两步法制作变应性鼻炎模型，同时设置正常对照组，仅给予致敏剂溶媒。豚鼠随机分为6组，即正常对照组、模型组、阳性药物（布地奈德鼻喷雾剂25.6μg/kg）组和rhIL-1ra 50、100和200μg/kg剂量组，每组10只动物。各给药组动物从激发前1 d（第8天，d 8）开始鼻腔给药，1次/d，连续14 d，正常对照及模型组动物相同方法给予rhIL-1ra溶媒。实验期间，按照临床评分标准对动物进行动态记录评分。待最后一次给药且临床评分结束后，麻醉并活杀动物，快速制备血清用于IgE水平测定；分离鼻黏膜组织用于组胺含量测定及组织病理学观察。结果与正常组比较，模型组豚鼠表现出典型的变应性鼻炎症状；与模型组比较，rhIL-1ra给药组动物的临床评分、喷嚏数、血清IgE水平、鼻黏膜组胺含量均显著降低（P＜0.05），且鼻黏膜组织病理学变化有显著改善。阳性药物组的表现与rhIL-1ra给药组基本相同，二者无显著性差异。结论成功建立了TDI诱发的变应性鼻炎豚鼠模型；在（50~200）μg/kg剂量范围内，rhIL-1ra显示出肯定的治疗效果，提示rhIL-1ra有望成为变应性鼻炎的新型防治药物。%Objective To evaluate the effects of the recombinant human interleukin-1 receptor antagonist(rhIL-1ra)on a tol⁃uene-2,4-diisocyanate(TDI)-induced guinea pig allergic rhinitis (AR)model. Methods An AR model was established via sensiti⁃zation and challenge of two-step procedure using TDI in guinea pigs. Normal animals were treated only with the olive oil(TDI vehicle). Sixty adult guinea pigs were randomly divided into six groups(n=10):normal group,model group(rhIL-1ra vehicle),positive con⁃trol group(budesonide,25.6μg/kg),rhIL-1ra treated groups(rhIL-1ra 50,100 and 200μg/kg,respectively). From day 8 after sensi⁃tization,animals of all the groups were treated respectively with the agents or vehicle once a day for 14 days. During the observation pe⁃riod,the index of clinic score was recorded for every animal. At day 14 of the dosing,guinea pigs were sacrificed 30 min after the last TDI challenge and observation. Blood samples were taken from the abdominal aorta to prepare the serum for detection of histamine , and the nasal mucosase were dissected for histamine detection and histopathological observation. Results Compared with the guinea pigs in normal group,those in the model group exerted the typical symptoms of AR. It was shown that rhIL-1ra could improve nasal symptoms and cause a significant decrease in the instances of nasal sneezing as well. In addition,rhIL-1ra significantly reduced the concentrations of histamine in the nasal mucosa and IgE in the blood compared with those in the model group(P<0.05). Moreover, the pathological results showed that less edema,vasodilation and inflammatory cell infiltration were found in the nasal mucosa after rhIL-1ra application. Budesonide also showed the above effects with no significant difference compared with rhIL-1ra. Conclusion A guinea pig allergic rhinitis model is successfully induced by TDI. The results indicated that rhIL-1ra(50-200μg/kg)is effective in im⁃proving allergic rhinitis. Our findings indicated that rhIL-1ra might serve as a potential new drug for allergic rhinitis therapy.
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