Xiao Peng, Hou Li, Liu Zhaohua, Mu Yanling, Liu Zengxiang, Wang Jiao, Qiu Shidong
Shandong Jianzhu University, Jinan, China.
Shandong Quality Inspection Center for Medical Devices, Jinan, China.
Mol Immunol. 2020 Apr 14;122:62-68. doi: 10.1016/j.molimm.2020.03.014.
Among a variety of traditional Chinese medicines, Shuanghuanglian injection (SHLI), has the highest incidence of injection-induced immediate hypersensitivity reactions (IHRs). However, the precise mechanisms of SHLI-induced IHRs remain to be understood. In the present study, we characteriszed IHRs as induced by SHLI by recording changes in physiological and hemodynamic indicators following intravenous injections of SHLI in rats and dogs. The results indicate that SHLI induced the release of histamine, decreased mean arterial blood pressure (MAP), increased SC5b-9 in rats and dogs, increased C4d and Bb in dogs without any changes in IgE. n vitro incubation of SHLI with serum from dogs in the presence of an inhibitor of complement activation (EGTA/Mg) resulted in an increase in C4d. These results suggest that SHLI induces anaphylactoid reactions in rats and dogs. Furthermore, SHLI appears to activate the complement system through classical and alternative pathways in dogs in vivo. Additional experiments in mice demonstrated that SHLI induces locus coeruleus infiltration and results in significant increase in vascular permeability within the skin of mice. We established a reliable method for the evaluation of anaphylactoid reactions induced by complex compounds, using multiple physiological indicators, different experimental models in vivo and in vitro.
在多种中药中，双黄连注射液（SHLI）引起注射诱导的即刻过敏反应（IHRs）的发生率最高。然而，SHLI诱导IHRs的确切机制仍有待了解。在本研究中，我们通过记录大鼠和犬静脉注射SHLI后生理和血流动力学指标的变化来表征SHLI诱导的IHRs。结果表明，SHLI诱导组胺释放，降低平均动脉血压（MAP），使大鼠和犬的SC5b-9升高，使犬的C4d和Bb升高，而IgE无任何变化。在补体激活抑制剂（EGTA/Mg）存在的情况下，SHLI与犬血清进行体外孵育导致C4d升高。这些结果表明，SHLI在大鼠和犬中诱导类过敏反应。此外，SHLI似乎在犬体内通过经典途径和替代途径激活补体系统。在小鼠中进行的额外实验表明，SHLI诱导蓝斑核浸润并导致小鼠皮肤内血管通透性显著增加。我们利用多种生理指标、体内和体外不同实验模型，建立了一种评估复杂化合物诱导类过敏反应的可靠方法。
