School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing 210023, China.
Molecules. 2016 Oct 12;21(10):1352. doi: 10.3390/molecules21101352.
Adverse reactions of injectable drugs usually occur at first administration and are closely associated with the dosage and speed of injection. This phenomenon is correlated with the anaphylactoid reaction. However, up to now, study methods based on antigen detection have still not gained wide acceptance and single physiological indicators cannot be utilized to differentiate anaphylactoid reactions from allergic reactions and inflammatory reactions. In this study, a reliable method for the evaluation of anaphylactoid reactions caused by injectable drugs was established by using multiple physiological indicators. We used compound 48/80, ovalbumin and endotoxin as the sensitization agents to induce anaphylactoid, allergic and inflammatory reactions. Different experimental animals (guinea pig and nude rat) and different modes of administration (intramuscular, intravenous and intraperitoneal injection) and different times (15 min, 30 min and 60 min) were evaluated to optimize the study protocol. The results showed that the optimal way to achieve sensitization involved treating guinea pigs with the different agents by intravenous injection for 30 min. Further, seven related humoral factors including 5-HT, SC5b-9, Bb, C4d, IL-6, C3a and histamine were detected by HPLC analysis and ELISA assay to determine their expression level. The results showed that five of them, including 5-HT, SC5b-9, Bb, C4d and IL-6, displayed significant differences between anaphylactoid, allergic and inflammatory reactions, which indicated that their combination could be used to distinguish these three reactions. Then different injectable drugs were used to verify this method and the results showed that the chosen indicators exhibited good correlation with the anaphylactoid reaction which indicated that the established method was both practical and reliable. Our research provides a feasible method for the diagnosis of the serious adverse reactions caused by injectable drugs which could be used in the clinical practice.
注射药物的不良反应通常在首次给药时发生，与剂量和注射速度密切相关。这种现象与类过敏反应有关。然而，到目前为止，基于抗原检测的研究方法仍然没有得到广泛的认可，并且单一的生理指标不能用于区分类过敏反应与过敏反应和炎症反应。在这项研究中，我们使用多种生理指标建立了一种可靠的评价注射药物引起的类过敏反应的方法。我们使用化合物 48/80、卵清蛋白和内毒素作为致敏剂来诱导类过敏、过敏和炎症反应。不同的实验动物（豚鼠和裸鼠）和不同的给药方式（肌肉内、静脉内和腹腔内注射）以及不同的时间（15 分钟、30 分钟和 60 分钟）进行评估，以优化研究方案。结果表明，通过静脉注射 30 分钟对豚鼠进行不同药物处理是实现致敏的最佳方式。此外，通过 HPLC 分析和 ELISA 测定检测了七种相关的体液因子，包括 5-HT、SC5b-9、Bb、C4d、IL-6、C3a 和组胺，以确定它们的表达水平。结果表明，在类过敏、过敏和炎症反应之间，其中 5-HT、SC5b-9、Bb、C4d 和 IL-6 这五个因子的表达水平有显著差异，这表明它们的组合可以用于区分这三种反应。然后使用不同的注射药物来验证这种方法，结果表明所选指标与类过敏反应具有良好的相关性，这表明所建立的方法既实用又可靠。我们的研究为诊断注射药物引起的严重不良反应提供了一种可行的方法，可用于临床实践。
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