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目的:探讨注射用双黄连(SHLI)发生类过敏反应的物质基础及其作用机制。方法:①类过敏反应和致类过敏物质研究:ICR小鼠随机分成不同实验组,分别一次性静脉注射含有0.4%伊文思蓝的不同浓度的SHLI、黄芩苷溶液、连翘苷溶液、绿原酸溶液、Compound 48/80溶液或生理盐水,给药后30 min记录各组动物耳廓血管通透性增高反应的阳性率,进行耳廓蓝染程度评分,并定量测定耳廓伊文思蓝渗出量。②类过敏机制研究:将小鼠分别预先口服不同剂量的息斯敏,腹腔注射环磷酰胺或Compound 48/80后,再静脉注射含有0.4%伊文思蓝的SHLI,同前述方法观察耳廓蓝染情况,将预处理组与同剂量SHLI组比较。结果:①SHLI 300,600 mg.kg-1(分别相当于临床剂量的等倍和2倍剂量)静脉注射均可引起小鼠耳廓血管通透性增高,耳廓明显蓝染;但相当于SHLI临床2倍剂量的连翘苷、黄芩苷和绿原酸静脉注射均未造成小鼠耳廓血管通透性增高。②预先口服息斯敏后,SHLI 600 mg.kg-1造成的小鼠耳廓血管通透性增高程度明显减轻;预先腹腔注射环磷酰胺后,血管通透性增高程度有轻度减轻,而预先腹腔注射Compound 48/80后,血管通透性增高程度没有明显变化。结论:SHLI在临床等效剂量和2倍临床剂量下有明显增高血管通透性的作用,提示有致类过敏作用。但SHLI的主要成分——连翘苷、黄芩苷和绿原酸可能不是造成SHLI发生类过敏反应的主要物质,SHLI发生类过敏反应的主要机制可能与直接刺激组胺的生成增加有关,白细胞激活可能参与了SHLI的致类过敏反应,抗组胺药可部分预防SHLI的类过敏反应。
Objective: To investigate the substance basis and mechanism of anaphylactoid reaction of Shuanghuanglian injection (SHLI). Methods: ①Analogue of allergic reactions and allergenic substances: ICR mice were randomly divided into different experimental groups and received intravenous injection of SHLI, baicalin solution, forsythin solution containing 0.4% Evans blue, Acid solution, Compound 48/80 solution or saline, 30 min after the administration, the auricle vascular permeability increased positive rate of each group was recorded, the score of auricle blue staining, and quantitative determination of auricle Evans blue Amount. ② Allergic mechanism: mice were preliminarily orally administered with different doses of astemizine, intraperitoneal injection of cyclophosphamide or Compound 48/80 followed by intravenous injection of SHLI containing 0.4% Evans blue. The same method as above was used to observe auricle blue Dye conditions, the pretreatment group and the same dose SHLI group. Results: (1) SHLI 300,600 mg.kg-1 (equivalent to twice the clinical dose and 2 times the dose of intravenous injection can cause increased auricular vascular permeability in mice, ears significantly blue stain; but the equivalent of SHLI clinical 2 Fold dose of forsythin, baicalin and chlorogenic acid intravenously did not cause increased auricle vascular permeability in mice. ② After pre-oral administration of astemizole, the increase of auricular vascular permeability in mice induced by SHLI 600 mg.kg-1 was significantly reduced. After intraperitoneal injection of cyclophosphamide, vascular permeability increased slightly, After pre-ip injection of Compound 48/80, there was no significant change in the increase of vascular permeability. Conclusion: SHLI can significantly increase the permeability of blood vessels in clinical equivalent dose and 2 times of clinical dose, suggesting that there is a kind of allergic effect. However, the main components of SHLI - forsythiaside, baicalin and chlorogenic acid may not be the main substances causing SHHI anaphylactoid reaction. The main mechanism of SHLI anaphylactoidism may be related to the direct stimulation of histamine production, leukocyte activation May be involved in SHLI induced allergic reaction, antihistamines can be partially SHLI allergic reactions.