苦碟子注射液(碟脉灵)过敏反应发生机制探讨

Underlying Mechanisms for Allergic Reactions of DML Ixeis Sonchifolia Hance Injection

目的:分析苦碟子注射液(碟脉灵,DML)过敏反应类型及可能产生的原因,对其过敏反应发生机制进行探索。方法:按照《中药、天然药物免疫毒性(过敏性、光变态反应)研究的技术指导原则》的实验方法对DML临床拟用剂量进行全身主动过敏实验(ASA)和皮肤被动过敏实验(PCA),并且采用酶联免疫吸附试验(ELISA)检测豚鼠血清总免疫球蛋白(Ig E),补体3(C3),补体4(C4),白细胞介素(IL)-4,IL-10,IL-2,前列腺素D2(PGD2),白三烯C4(LTC4),肿瘤坏死因子-α(TNF-α),干扰素-γ(IFN-γ)水平的变化。结果:ASA过敏症状,激发后卵白蛋白组症状表现均为极强阳性(死亡)。DML未超滤组较氯化钠组与超滤组症状反应均强烈(P<0.01)。血清免疫学指标改变:与氯化钠组比较,DML未超滤组血清中总Ig E,IL-10,LTC4,TNF-α,IFN-γ,IL-2均有明显升高(P<0.05,P<0.01),DML超滤组血清PGD2,TNF-α,IFN-γ均明显升高(P<0.05,P<0.01)。与DML超滤组比较,未超滤组血清中总Ig E,IL-4均有明显升高(P<0.05,P<0.01)。PCA:氯化钠组蓝斑阳性率为0,与卵蛋白组比较,DML未超滤组与DML超滤组小鼠蓝斑直径均减小(P<0.05,P<0.01);与氯化钠组、DML超滤组比较,DML未超滤组吸光度A显著升高(P<0.01),与超滤组比较,卵蛋白组A显著升高(P<0.01)。结论:由Ig E介导的Ⅰ型过敏反应是DML发生过敏反应的主要类型,其主要发生机制可能为DML所含大分子物质通过Ig E介导免疫激发体内各类炎症介质释放,产生免疫反应,减少大分子物质可能是防止DML发生过敏反应的重要途径。

Objective： To analyze the types and main potential causes of Diemailing（ DML） allergic reactions,and explore the underlying mechanisms of such allergic reactions. Method： According to the Guideline for Immunotoxicity Research（ Allergy and Photoallergic Reaction） on Chinese Medicine and Natural Medicine,the active systemic anaphylaxis（ ASA） test and passive cutaneous anaphylaxis（ PCA） test were carried out for DML ixeis sonchifolia hance injection. Serum Ig E, C3, C4, interleukin（ IL）-4, IL-10, IL-2, prostaglandin D2（ PGD2）,leukotriene C4（ LTC4）,tumor necrosis factor（ TNF）-α and interferon（ IFN）-γ levels were determined by using ELISA. Result： ASA allergic symptoms,after stimulation,the ovalbumin group experienced the strongest positive symptom（ death）. The allergic symptoms of the non-ultrafiltrated DML group were stronger than those of the sodium chloride injection group and the ultrafiltrated DML group（ P〈0. 01）. Changes in serum immunological parameters： Compared with the sodium chloride injection group,some indexes in serum of the nonultrafiltrated DML group were increased significantly such as Ig E,IL-10,LTC4,TNF-α,IFN-γ and IL-2（ P〈0. 05,P〈0. 01）,and the levels of PGD2,TNF-α and IFN-γ in ultrafiltrated DML group were also increased significantly（ P〈0. 05,P〈0. 01）. Compared with the ultrafiltrated DML group,Levels of serum Ig E and IL-4 of the non-ultrafiltrated DML group were significantly increased（ P〈0. 05,P〈0. 01）. PCA： Positive rate of blue spots is zero in the sodium chloride injection group. Compared with the ovalbumin group,the diameters of blue spots were significantly decreased in both non-ultrafiltrated DML group and ultrafiltrated DML group（ P〈0. 05,P〈0. 01）. Compared with the sodium chloride injection group and ultrafiltrated DML group,the absorbance（ A）of the non-ultrafiltrated DML group was significantly increased（ P〈0. 01）. The A of the ovalbumin group was significantly increased than that of the ultrafiltrated DML group（ P〈0. 01）. Conclusion： Type I allergy mediated by Ig E is the main type of DML injection＇s allergic reactions. The macromolecular substance in DML can release various inflammatory mediators through Ig E mediated immune stimulation. This kind of immunity reaction may be the main mechanism of allergic reactions in DML,so reducing macromolecular substances may be an important way to prevent allergic reactions of DML.