中药注射剂类过敏反应临床前评价:动物品系和性别差异研究

类过敏反应在首次用药后发生,与过敏反应需要抗原致敏后再次激发2个阶段的致病机制不同。该研究探讨2种中药注射剂诱导不同品系和性别小鼠发生的类过敏反应,为小鼠类过敏反应检测模型在动物品系和性别上的选择提供依据。用ICR,昆明,BALB/C,C57小鼠进行2种中药注射剂的类过敏试验,比较4种小鼠的敏感性,并比较雌雄性动物的差异。各小鼠均一次性静脉注射含有0.8%伊文思蓝(EB)的受试物,以耳廓蓝染发生率和EB渗出量作为类过敏反应评价指标。在ICR和昆明小鼠上,2种中药注射剂通过静脉注射给药均在一定剂量下诱导出类过敏反应,在同种注射剂同剂量下ICR的类过敏反应更明显,说明ICR小鼠更敏感。只有1种注射剂在BALB/C小鼠上呈现出了类过敏反应,且反应程度较ICR和昆明小鼠明显减弱;2种注射剂在C57小鼠上均未诱导出类过敏反应。雌雄动物比较结果显示,1种注射剂雌雄动物未见明显差异,而另一种注射剂雄性动物比雌性动物敏感。因此,进行中药注射剂小鼠类过敏试验,ICR小鼠是较为理想的试验品系,应该作为首选动物;其次可选用昆明小鼠。BALB/C和C57小鼠敏感性较低,不建议用于中药注射剂类过敏试验。中药注射剂对小鼠类过敏反应显示有一定雌雄性别差异,雄性小鼠更为敏感。

Preclinical evaluation of pseudoallergic reactions on Chinese herbal injections: study on animal strain and gender difference

Pseudoallergic reactions occured after the first administration of patients, and the pathogenic mechanisms of them were different from the allergic reactions which needed excitation after antigen sensitization. To provide a basis for evaluation, clinical use and drug development of pseudoallergic reactions, the models were established by two kinds of Chinese herbal injections (CHI) both on different strain or gender mice. With the use of ICR, Kunming, BALB/C, C57 mice, pseudoallergic tests of two CHI were conducted to compare the sensitivity of four strains mice, and compared the differences in male and female animals. Test substances contain 0.8% Evans blue (EB) were intravenously injected into different strain and gender mice. Scores of ear blue staining and quantitation of ear EB exudation were the parameters for pseudoallergic reaction. Results of strain difference indicated that both CHI A and B could cause severe pseudoallergic reactions indicated by obvious vascular hyperpermeability on ICR mice. The pseudoallergic reactions in ICR mice are more obvious under the the same dose of injection, which stated the sensibility of ICR mice. And the reactions of KM mice and BALB/C mice were slightly reduced which compared to ICR mice, even alomost nothing on C57 mice. Comparison results of gender difference showed that one CHI was not have significant difference in male and female animals, but male animals were more susceptible than females on another CHI. Therefore, ICR mice were preferable experimental strain on the model of pseudoallergic reactions induced by CHI A and B. Because of female animals were easily influenced by estrous cycle, the pseudoallergic reactions induced by CHI A and B select and use male mice befittingly.