用清醒Beagle犬进行中药注射液的类过敏试验方法研究

目的:探讨中药注射剂类过敏试验方法,以用于中药注射剂类过敏反应的临床前评价。方法:将Beagle犬随机分成对照组(C)、0.5%聚氧乙烯脱水山梨醇单油酸酯(吐温80)组(T)、含0.5%吐温80鱼腥草注射液组(TY)、无吐温80鱼腥草注射液组(Y)。上述各组分别注射各自受试药3 mL.kg-1。给药后立即开始观察动物的反应,并于注射后10,30 min分别测定血压、呼吸、心率。结果:T组和TY组动物注射后很快出现局部红肿,由于瘙痒而烦躁不安,挠耳或挠头、搔鼻、舔舌等"过敏反应"症状,有的动物出现皮肤湿冷、步态不稳或跌倒、精神萎靡或静卧、嗜睡、流涎、流泪、呼吸急促或喘息、紫绀等;有的动物有多次排便、排尿反应。T组和TY组动物也在给药后很快出现血压显著降低,呼吸和心率增快。以上症状与临床上人的过敏反应相似。而C组和Y组动物未见异常反应,血压、呼吸和心率无显著改变。结论:Beagle犬可作为临床前评价中药注射剂类过敏反应的动物模型。该模型与临床具有高度的一致性,模型敏感、重复性好、可操作性强、结果评价简便客观。

Pseudoanaphylactoid reaction analysis of Chinese herbal injections in Beagle dogs

Objective : To investigate the preclinical evaluation method of pseudoanaphylactoid reactions for Chinese herbal injections. Method : Beagle dogs were divided into control group (C), 0.5% tween 80 group (T),Yuxincao injection containing 0.5% tween 80 (YT), distilled solution from Yuxincao(Y). Various groups of Beagle dogs were given 3 mL·kg^-1 of the test articles intravenously. The anaphylactoid reactions were observed immediately, while blood pressure, respiratory frequencies and heart rates were tested at 10 min and 30 min after administration. Result : A variety of symptoms that range from cutaneous and mucosa signs to bronchospasma and cardiovascular collapse, including angioedema at lip, conjunctiva, ear and circumoral skin, somnolence, lethargy, breathless or dyspnea, severe hypotension etc were observed in T and TY groups from immediately post-injection to at least 30 min after administration. These reactions occurred at both first injection or repeated injections at 2-4 weeks intervals, manifesting that it was pseudoanaphylactoid reaction mediated by non-immune mechanisms. Conclusion : Beagle dogs could be used as an animal model for preclinical evaluation of pseudoanaphylactoid reactions of Chinese herbal injection with sensitivity, reproducibility, and high clinic consistency.