大分子杂质是双黄连注射剂导致类过敏反应的重要原因(英文)  

Macromolecules in Shuanghuanlian Injection are an Important Cause of Anaphylactoid Reaction

作　　者：万绪莲 夏恒 韩依伦 李律宇 陈欢 黎勇坤 段为钢 WAN Xulian;XIA Heng;HAN Yilun;LI Lvyu;CHEN Huan;LI Yongkun;DUAN Weigang(School of Basic Medicine,Yunnan University of Chinese Medicine,Kunming 650500,China;College of Traditional Chinese Medicine,Yunnan University of Chinese Medicine,Kunming 650500,China;The Third Affiliated Hospital,Yunnan University of Chinese Medicine,Kunming 650500,China)

机构地区：[1]云南中医药大学基础医学院,云南昆明650500 [2]云南中医药大学中药学院,云南昆明650500 [3]云南中医药大学第三附属医院,云南昆明650500

出　　处：《云南中医学院学报》2022年第3期41-52,共12页Journal of Yunnan University of Traditional Chinese Medicine

基　　金：云南省应用基础研究项目(2018FF001-002,202101AZ070001-010,202101AZ070001-093)。

摘　　要：目的双黄连注射液(SHL)是常发类过敏反应的中药注射剂之一,本文以阳性药化合物48/80(C48/80)为参照发现并证明外源性大分子物质是导致类过敏反应的重要原因。方法将C48/80和双黄连注射液(原液)用10 kDa分子筛制备成组分A(富含10 kDa以上大分子物质)和组分B(不含10 kDa以上大分子物质)。将原液、组分A和组分B于豚鼠进行常规被动皮肤类过敏试验和大鼠肺灌流血管通透性检查。结果C48/80原液中大分子物质占10%以上,SHL的确含有有色的大分子物质。C48/80或SHL的组分A单次静脉注射可导致豚鼠发生严重类过敏反应。C48/80组分A可导致肥大细胞脱颗粒,而SHL的组分A未见该现象。在被动皮肤类过敏试验中,C48/80和SHL的组分A均可导致豚鼠发生明显阳性反应,这种反应均可被色甘酸钠部分对抗。在大鼠肺脏灌流实验中,C48/80和SHL的组分A可明显增加肺毛细血管的通透性,该作用也可被色甘酸钠对抗。在以上实验中,组分B很少导致阳性反应,如果发生也明显表现轻微。结论C48/80和SHL中的大分子物质是导致静脉注射发生类过敏反应的重要原因,其机理涉及到血管通透性增加。Objective Shuanghuanglian injection(SHL)frequently occurs anaphylactoid reactions.The main aim of the present study was to investigate that injected exogenous macromolecules are an important cause for anaphylactoid reactions using C48/80,a tool agent.Methods Component A(rich in macromolecules above 10 kDa)and component B(free of substances above 10 kDa)were prepaired from the original C48/80 or the original injection.The original,component A and component B from C48/80 or SHL were uesed for routine anaphylactoid test in rabbits and guinea pigs,and for pulmonary capillary permeability examination in rats.Results The original C48/80 contain more than 10%substances above10 kDa,and SHL contained colored macromolecules.Component A from C48/80 or SHL caused a strong anaphylactoid reaction in guinea pigs by intravenous administration.Component A from C48/80 triggered mast cell degranulation while that from SHL did not.In addition,component A from C48/80 and SHL cuased a similarly strong passive cutaneous anaphylactoid(PCA)reaction,and also caused a strong pulmonary capillary permeability.The PCA reaction and permeability caused by component A both from C48/80 and SHL were largely prevented by cromolyn sodium.Nevertheless,component B containing substances below 10 kDa almost caused no anaphylactoid reactions;if happened,much weaker.Conclusion All the results suggested that injected macromolecular substances are one of the main factors responsible for anaphylactoid reactions caused both by C48/80 and SHL.The increase of vascular permeability participates the anaphylactoid reactions ignited by C48/80 and SHL.

关 键 词：类过敏反应 大分子物质 化合物48/80 双黄连注射液 毛细血管通透性 被动皮肤类过敏试验 

分 类 号：R285[医药卫生—中药学]