基于BN大鼠动物模型的注射用丹参多酚酸致敏性研究  

Sensitization research of Salvianolic Acids for Injection on BN rat model

作　　者：张瀛化 张家丰 万梅绪[3,4] 李智 张燕欣 李德坤 杨晓英[1] 鞠爱春 ZHANG Yinghua;ZHANG Jiafeng;WAN Meixu;LI Zhi;ZHANG Yanxin;LI Dekun;YANGXiaoying;JU Aichun(School of Pharmacy,Tianjin Medical University,Tianjin 300070,China;Tripod(Nanjing)Clinical Research Co.,Ltd.Nanjing 210000,China;Tianjin Tasly Pride Pharmaceutical Co.,Ltd.,Tianjin 300410,China;Tianjin Key Laboratory of Safety Evaluation Enterprise of Traditional Chinese Medicine Injections,Tianjin 300410,China)

机构地区：[1]天津医科大学药学院,天津300070 [2]鼎泰(南京)临床医学研究有限公司,江苏南京210000 [3]天津天士力之骄药业有限公司,天津300410 [4]天津市中药注射剂安全性评价企业重点实验室,天津300410

出　　处：《药物评价研究》2020年第8期1565-1569,共5页Drug Evaluation Research

基　　金：天津市科技重大专项与工程(18ZXXYSY00120)。

摘　　要：目的通过BN大鼠全身主动过敏实验考察注射用丹参多酚酸的过敏反应症状,检测致敏后BN大鼠血清中的IgE、组胺及β-氨基己糖苷酶含量,考察注射用丹参多酚酸是否产生速发型过敏反应。方法以卵白蛋白为阳性药物、生理盐水为对照,注射用丹参多酚酸分为低、中、高(13.43、26.86、134.30 mg/kg)3个剂量组分别直接对BN大鼠进行致敏和激发,观察过敏反应症状;酶联免疫吸附法(ELISA)法检测致敏后动物血清中的IgE、β-氨基己糖苷酶及组胺的含量变化;激发后的BN大鼠立即处死,取肺组织进行HE染色。结果 BN大鼠全身主动过敏实验中仅卵白蛋白组有明显过敏反应;与对照组比较,BN大鼠致敏血清IgE水平仅卵白蛋白组显著升高(P<0.05),组胺检测各组间均无显著性差异,注射用丹参多酚酸中、高剂量组β-氨基己糖苷酶释放量显著降低(P<0.05);BN大鼠激发后,肺部组织病理结果仅阳性药组肺泡壁凝固性坏死,肺间质有大量炎症因子浸润。结论注射用丹参多酚酸未产生由IgE介导的I型过敏反应。Objective Investigating the allergic reaction of Salvianolic Acids for Injection(SAFI)by active systemic anaphylaxis in BN rats.detecting the content of IgE,histamine andβ-hexosaminidase in the serum of BN rats after sensitization for investigating whether the allergic reaction is immediate hypersensitivity.Methods ovalbumin(OVA)was used as positive drug group,strokephysiological saline solution was used as negative control group,and injection dose of SAFI was divided into low,medium and high(13.43,26.86,134.30 mg/kg)groups to sensitize and stimulate BN rats directly,then observing the symptoms of allergic reaction.Enzyme linked immunosorbent assay(ELISA)was used to detect the content of IgE,β-hexosaminidase and histamine in serum of sensitized animals.After stimulation,BN rats were immediately sacrificed to obtain lung tissue for pathological study.Results BN rats had no significant difference between drug groups and negative control group in allergic reaction except positive group.In the sensitized serum of BN rats,The result of Enzyme linked immunosorbent assay show that IgE content of positive has significant difference from the rest of the groups.And there was no significant difference among all test groups in detecting the content of histamine.The release content ofβ-hexosaminidase test in the medium dose group and the high dose group was significantly different with other groups.And the concentration of SAFI was negatively correlated with the release content ofβ-hexosaminidase.The results of Hematoxylin-Eosin show that the positive group had coagulation necnosis of alveolar wall and extensive inflammatory factor infiltration in the lung stroma,while all the other groups were normal.Conclusion The results indicated the SAFI may not cause anaphylaxis reaction in BN rats modle,long-term administration of the drug will not cause increasing(IgE,histamine andβ-hexosaminidase)indexes in vivo.

关 键 词：注射用丹参多酚酸 全身主动过敏 BN大鼠 IGE 组胺 β-氨基己糖苷 

分 类 号：R965.3[医药卫生—药理学]