注射用双黄连与生脉注射液对Hartley豚鼠与BN大鼠主动全身过敏反应的影响

目的:研究注射用双黄连、生脉注射液对Hartley豚鼠与棕色挪威(BN)大鼠的主动全身过敏反应(active systemic anaphylaxis,ASA)及其相关指标,为完善中药注射剂过敏性评价提供实验依据。方法:取Hartley豚鼠或BN大鼠随机分为卵蛋白(OVA)组、注射用双黄连(双黄连)组、生脉注射液(生脉)组、正常组。2种动物分别隔日ih受试药物致敏液3次,于致敏后第14天静脉注射相应的激发液,观察激发后30 min动物的全身过敏反应症状,苏木素-伊红(HE)染色观察肺组织病理改变。放射免疫法检测BN大鼠在致敏前及激发后血清总免疫球蛋白E(Ig E)水平的变化、致敏激发后血清类胰蛋白酶变化。结果:对Hartley豚鼠或BN大鼠,OVA组、双黄连组动物均呈现过敏反应症状,肺组织病理切片显示均有明显淋巴细胞浸润等炎症病理表现,但双黄连组较轻。生脉组则未见过敏反应症状以及肺组织病理异常。与正常组比较,OVA组、双黄连组、生脉组大鼠激发后血清总Ig E水平显著升高(P0.05,P0.01)。与致敏前同组动物血清总Ig E水平比较,激发后OVA组、双黄连组血清总Ig E水平显著升高(P0.05,P0.01)。与正常组比较,OVA组、双黄连组大鼠激发后血清类胰蛋白酶水平显著升高(P0.01,P0.05),生脉组有升高趋势,但是无显著差异。结论:采用不同品种实验动物及增加相关检测的指标,能更全面评价注射用双黄连、生脉注射液潜在的致敏性。

Active Systemic Anaphylaxis to Shuanghuanglian and Shengmai Injection in Hartley Guinea Pigs and BN Rats

Objective: To study the active systemic anaphylaxis (ASA) and relevant indicators induced by Shuanghuanglian and Shengmai injection in Hartley guinea pigs and Brown Norway(BN) rats. Method: Hartley guinea pigs or BN rats were randomly divided into ovum albumin (OVA) group, Shuanghuanglian injection group, Shengmai injection group and normal group. Animals were injected with test sensitization drug liquid 3 times every other day. On day 14 of sensitization, corresponding arousal liquid was intravenously injected. The usual systemic symptoms of ASA test were observed within 30 min after the last injection. The lung tissue pathological examination was performed with hematoxylin-eosin(HE) staining. Changes of serum immunoglobulin E(IgE) levels before sensitization and after arousal, and changes of serum tryptase after sensitization and arousal were determined using radioimmunoassay in BN rats. Result: Hartley guinea pigs or BN rats in OVA group and Shuanghuanglian injection group showed systemic allergy symptoms. The pathological changes of the lung tissue with perivascular lymphocyte infiltration were observed, but the symptoms in Shuanghuanglian group were less serious. Shengmai group had no anaphylaxis or pathological abnormality of lung tissues. Compared with the normal group, the levels of serum IgE were significantly increased in OVA group, Shuanghuanglian group and Shengmai group after arousal (P<0.05, P<0.01). Compared with the animals of the same group before arousal, the total serum IgE levels after arousal were significantly increased both in OVA group and Shuanghuanglian group (P<0.05, P<0.01). Compared with the normal group, the serum tryptase levels in OVA group and Shuanghuanlian group were significantly increased after arousal (P<0.01, P<0.05), and Shengmai group had an increase trend but with no significant difference. Conclusion: Application of different animal species and increasing relevant detection indicators are useful to more comprehensively evaluate the potential ASA induced by Shuanghuanglian and Shengmai injection.