中药注射剂降压物质检查结果与类过敏反应的相关性研究

目的: 为应用降压物质检查法控制中药注射剂的类过敏反应提供理论和实验依据。方法: 以小鼠耳廓蓝染试验筛选得到能引发类过敏反应的清开灵注射液,以降压物质检查法检查其引发家猫血压下降的能力,以豚鼠回肠体外收缩的试验检查其中组胺类物质的含量,以肥大细胞膜稳定剂色甘酸钠研究其引发类过敏反应的机理。结果: 小鼠耳廓蓝染试验阳性结果的清开灵注射液降压物质检查结果也为阳性,豚鼠回肠体外收缩的试验结果则为阴性,提示具有引发类过敏反应能力的清开灵注射液中不含组胺类物质,肥大细胞膜稳定剂色甘酸钠则可以显著抑制清开灵注射液所引发类过敏反应。结论: 中药注射剂在不含有组胺类物质的情况下也可以表现出降压物质检查阳性的结果,可能是通过直接刺激体内肥大细胞脱颗粒释放内源性组胺而导致的,该反应过程与类过敏反应的病理过程高度接近,以上结果提示降压物质检查法有望应用于中药注射剂引发类过敏反应的质量控制。

Objective: To provide theoretical and experimental evidence for depressor substances test to inspect the anaphylactoid reactions in traditional Chinese medicine injection (TCM) quality control. Methods: Qingkailing injection that could cause anaphylactoid reaction was selected by using mice ear blue dye test.The ability to trigger blood pressure drop was determined in domestic cats, the contents of histamine materials were examined using guinea pig ileum in vitro contraction test, and the mechanism of its allergic reactions was studied in mast cell with membrane stabilizer sodium cromoglycate. Results: Qingkailing injection that was positive in mice ear blue dye analysis also showed positive result in depressor substances test in cat, while it showed negative result in guinea pig ileum contraction test.These results suggested these Qingkailing injections do not contain histamine-like substances.Moreover, the mast cell stabilizer, sodium cromoglycate, was shown to be able to significantly suppress the mice ear blue dye reactions of the Qingkailing injection and Tween 80. Conclusion: TCM injection without histamine-like substance also can cause cat blood pressure drop, which might function through the mast cells degranulation and release the inner histamine.This progress is very similar to the anaphylactoid reaction pathological progress.Taken together, our findings suggested that depressor substances test in cat be used to detect the anaphylactoid reaction for TCM injection.