TDI诱发变应性鼻炎豚鼠模型的建立

Establishment and characteristics of a TDI-induced model of allergic rhinitis in guinea pigs

目的建立甲苯-2,4-二异氰酸酯(TDI)诱发的变应性鼻炎(AR)豚鼠模型。方法模型组和布地奈德治疗组动物,利用10%的TDI经鼻通过反复致敏和激发两个步骤诱发AR模型。致敏和激发均采用TDI双侧鼻孔滴鼻(每侧鼻孔以12.5μl/kg计算),其中,致敏过程共7 d,每天1次;激发过程共14 d,隔天1次。自致敏开始,记录动物临床评分和喷嚏数。待实验结束后,分离鼻黏膜并制备血清,观察鼻黏膜组织病理学变化,检测鼻黏膜组胺含量及血清中IgE含量。布地奈德治疗组动物,自致敏结束次日开始通过双侧鼻孔滴鼻给药(每侧鼻孔给药为10μl/kg),每天1次,连续14 d;模型组按相同方式给予等体积生理盐水。正常对照组动物,以橄榄油替代10%TDI,其余处理同模型组。结果与正常对照组比较,模型组豚鼠的临床评分、鼻黏膜组织组胺含量及血清IgE含量均明显升高(P<0.05),鼻黏膜组织出现嗜酸性粒细胞浸润、小血管扩张、组织水肿及上皮脱落等典型的炎性病理变化;布地奈德给药则可显著改善以上病变。结论 TDI在豚鼠体内能够诱发典型的变应性鼻炎模型,具有方法简便可靠、成功率高的优点。

Objective To establish an allergic rhinitis （AR） model of guinea pigs induced by 2,4- toluene diisocyanate （TDI）. Methods The AR model of guinea pigs were induced by intranasal instillation with 10% TDI solution through the two steps of sensitization and challenge consequently. For the sensitization, animals were intranasal instillated with 10% TDI at a dose of 12.5 p.l/kg in each nasal hole one time per day for 7 days. For the challenge, animals were treated with the same method from the 8th day but one time the other day for 14 days. From the first day of the sensitization, clinical scores of the animals were recorded everyday till the end of the challenge. When the records were completed, the nasal mucosa of guinea pigs was dissected for the pathological observation and the blood was collected from the abdominal aorta for the detection of IgE. For e- valuation of the responses of the model animals to drug treatment, budesonide was intranasal instillated at 10 p^l/ kg each nasal hole one time per day from the 8th day to the 20th day. Accordingly, the normal group of guinea pigs was intranasal instillated olive oil instead of 10% TDI but the others the same as the model group. Results Compared with that of the normal group, guinea pigs of the model group were increased markedly in their clin- ical scores, levels of the nasal mucosa histamine and blood IgE （ P 〈 0.05 ）, and shown some pathological altera- tions such as vasodilatation, hyperplasia of glands, edema and increased eosinophil infiltration in the lamina pro- pria of the nasal mucosa, and part of epithelium mucosa exuviated levels increased after challenges. However, the budesonide treatment could improve the above changes of guinea pigs of the model group. Conclusion The guinea pig model of allergic rhinitis can be induced by TDI intranasal instillation. The method was simple, timesaving and must be useful in the study of allergic rhinitis.