抗组胺药物对运动性哮喘豚鼠模型的作用

Efficacy of Antihistamine Drugs on the Model for Exercise-Induced Asthma in Guinea Pigs

目的研究两种抗组胺药物———氯雷他定和酮替芬对于用脂多糖和甲吡丙酮介导的运动性哮喘豚鼠模型的作用。方法19只豚鼠用脂多糖和甲吡丙酮注射。他们被随机分成三组:对照组(n=7)不服药,酮替芬组(n=6)口服酮替芬1 mg/(kg.d),氯雷他定组(n=6)口服氯雷他定2 mg/(kg.d),连续4 d。第5天,分别在运动前后测量3组的肺阻力(RL)及呼吸系统的动态顺应性(Cdyn)。三组的支气管肺泡灌洗液(BALF)进行白细胞计数及分类。检查肺的形态。结果对照组,有RL显著增加和Cdyn显著降低。在酮替芬及氯雷他定组RL及Cdyn都没有这种变化,对照组的BALF中性粒细胞、巨噬细胞及嗜酸性粒细胞计数明显增加。形态学研究显示对照组的支气管黏膜有中性粒细胞浸润。结论在用脂多糖和甲吡丙酮预处理的运动性哮喘豚鼠模型中,氯雷他定和酮替芬能够抑制支气管收缩。抑制气道炎症的形成可能是这些H1受体拮抗剂的治疗机制。

Objective To investigate the effects of antihistamine agents, loratadine and ketotifen, on the model of exercise-induced asthma in guinea pigs induced by lipopolysaccharide （LPS） and metyapone. Methods 19 guinea pigs were injected with LPS （1 mg/kg, i.p. ） and metyapone （50 mg/kg, i.p. ）. Then they were divided into 3 groups randomly. In the control group （ n = 7）, they did not take any drug; in ketotifen group （ n =6）, they were administered orally ketotifen （1 mg/kg/day） and in loratadine group （n = 6）, they were administered orally with loratadine （2 mg/kg/day） for4 days. On the fifth day, lung resistance （RL） and dynamic compliance of respiratory system （Cdyn） of 3 groups were measured before and after exercise challenge. The total number of leukocytes in bronchoalveolar lavage fluid （BALF） from 3 groups was counted and differentiated cell type count was made. Morphometric examination of the animal lungs was performed. Results In control group, RL increased and Cdyn decreased significantly after exercise challenge. In ketotifen group and loratadine group there were no such changes either in RL or in Cdyn. There was a significant increase in the number of neutrophils, macrophages and eosinophils in BALF from control group. The infiltration of neutrophils in the bronchial mucosa was shown in control group in the morphometric study. Conclusion Loratadine and ketotifen can inhibit the exercise-induced bronchoconstriction in guinea pigs pretreated with LPS and metyrapone. Inhibiting the formation of inflammation in airway may be the therapeutic mechanism of these H-1 receptor antagonists.