3种中药注射剂类过敏反应评价及其机制探讨

Evaluation and study of pseudo-allergic reactions of three kinds of traditional Chinese medicine injections and its mechanisms

该文以不良反应报道较多的3种中药注射剂——鱼腥草、生脉和清开灵注射液为代表,借助小鼠类过敏反应模型,将含有0.4%伊文思蓝(EB)的各中药注射剂、阴性和阳性对照一次性静脉注射入小鼠体内,30 min后,比较各组小鼠耳廓蓝染情况,以对中药注射剂的类过敏反应进行评价;另外单独将各中药注射剂静脉注射入小鼠体内,分别于5 min和30 min后取血浆和血清,ELISA法测定其中的组胺,VEGF,TNF-α和IL-10的含量,并对耳和肺组织进行组织病理学检测,从而探讨其可能的类过敏反应机制。结果显示除鱼腥草注射液外,临床1.5倍和3.3倍浓度的生脉和清开灵注射液均可以引发小鼠发生以血管通透性增高为主要表现的轻微类过敏反应,低于此浓度则不发生;另外这2种注射液均导致小鼠血中组胺含量明显升高(P<0.05,P<0.01),但VEGF,TNF-α和IL-10含量变化不明显,提示生脉和清开灵注射液诱发ICR小鼠的类过敏反应发生可能与组胺释放增加有关。组织病理检查可见,各致敏注射液组小鼠耳、肺组织呈现明显的炎性改变;因此研究初步认为炎性机制导致的血管通透性增高是中药注射剂的类过敏反应主要原因。

To evaluated the pseudo-allergic reactions of cordate houttuynia, pulse-activating and Qingkailing injection in mice, the ICR mouse were divided into different test groups, then were intravenously injected with three traditional Chinese medicine injections, positive control compound 48/80 and physiological saline as normal control. All test substances were mixed with 0. 4% Evans blue. The reaction and vascular permeability of the ears were observed and measured 30 min after injection. At the same time, the mechanisms of the traditional Chinese injections＇ pseudo-allergic reactions was studyed. ICR mice were injected with the test substances as above without EB, blood in a part of mice were collected after 5 min, and the level of histamine in the plasma were measured. Blood in the other part of mice were coUected after 30 min, and the level of VEGF, TNF-α and IL-10 in the serum were measured. The reasults showed that except the eordate houttuynia injection, pulse-activating injection in 1.5 times clinical concentration and Qingkailing injection in 3.3 times clinical concentration caused mild pseudo-allergic reactions mainly for vascular permeability, no pseudo-allergic reactions occurred when the concentration of the two injections was below the concentration metioned above ; 5 minutes after intravenous injection of the three TCM injections into ICR mice with the highest dose, the levels of histamine in plasma of pulse-activating injection and Qingkailing injection groups were increased significantly, 30 minutes later, the levels of VEGF, TNF-α and IL-10 in the serum of all groups were no significant change compared to normal group. The mouse of pulse-activating and Qingkailing injection groups showed inflammatory changes in ear and lung tissues. It can be conluded that when the dose or concentration increased to a certain extent, pulse-activating and Qingkailing injec tion could induce pseudo-allergic reactions on ICR mice, the increased histamine realease maybe the main reason for pseudo-allergic reac- tions of the two traditional Chinese medicine injections. In addition the author preliminary thought that inflammatory mechanisms leading to hyperpermeabilities were the main reason of the traditional Chinese medicine injection＇s pseudo-allergic reaction.