胆碱酯酶抑制剂沙林诱发犬循环衰竭时血液内心血管活性物质的变化以及抗毒剂的对抗效应

中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (3): 266-269.

胆碱酯酶抑制剂沙林诱发犬循环衰竭时血液内心血管活性物质的变化以及抗毒剂的对抗效应

龙超良, 王汝欢¹, 张雁芳, 李军, 汪海

军事医学科学院毒物药物研究所,北京 100850;
¹北京恩华医药研究院,北京 100039

收稿日期:2005-12-02 修回日期:2006-01-02 出版日期:2006-03-26 发布日期:2020-12-04
通讯作者: 汪海,男,研究员,博士生导师,主要从事心血管药理和新药研究。Tel:010-66932651 E-mail:wh@nic.bmi.ac.cn
作者简介:龙超良,男,医学博士,副研究员,主要从事心血管药理学研究。Tel:010-66931557 E-mail:longchaoliang@sohu.com

Changes of plasma vascular active substances in dog circulation failures induced by cholinesterase inhibitor sarin and therapeutic effects of antidotal treatment

LONG Chao-liang, WANG Ru-huan¹, ZHANG Yan-fang, LI jun¹, WANG Hai

Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China;
¹Beijing Enhua Academy of Medicine,Beijing 100039,China

Received:2005-12-02 Revised:2006-01-02 Online:2006-03-26 Published:2020-12-04

摘要/Abstract

摘要： 目的在胆碱酯酶抑制剂沙林所致的犬循环衰竭模型上,观察循环衰竭前后及N受体拮抗剂美加明与M受体拮抗剂阿托品救治后,动物血液内心血管活性物质的变化情况。方法 20只健康成年雄性杂种犬,体重12~15kg。随机分为4组,对照组、阿托品组、美加明组和阿托品与美加明联用组。肌肉注射沙林诱发循环衰竭模型,以氯解磷定10mg·kg^-1为底药,观察循环衰竭前后血液内心血管活性物质的变化以及药物的影响。结果与染毒前相比,沙林诱发犬循环衰竭时,血液中舒血管活性物质一氧化氮(NO)、前列腺环素(PGI₂)和心房肽(ANP)以及缩血管活性物质血管紧张素Ⅱ(AngⅡ)、内皮素(ET)和血栓素A₂(TXA₂)均显著增高(P<0.01),美加明与阿托品合用治疗15min时,上述心血管活性物质即显著下降(P<0.05),60min时基本恢复正常,疗效均明显好于单用阿托品、美加明组。结论血浆NO、PGI₂、ANP、AngⅡ、ET和TXA₂等心血管活性物质的升高水平与胆碱酯酶抑制剂沙林诱导的犬循环衰竭程度及病情转归相关,美加明与阿托品合用,抗毒作用显著增强。

关键词: 胆碱酯酶抑制剂, 沙林, 循环衰竭, N受体拮抗剂, 美加明, 阿托品, 心血管活性物质

Abstract: AIM: To investigate the changes of plasma vascular active substances before and after treatment with neuronal nicotinic receptor antagonist mecamylamine or muscarinic receptor antagonist atropine against the circulation failures induced by the cholinesterase inhibitort sarin in dogs.METHODS: Twenty healthy adult male dogs,weighing 12-15 kg,were divided into four groups randomly:control;treatment with mecamylamine;treatment with atropine and treatment with mecamylamine and atropine at the dose ratio of 1∶10(n=5).Animals were given intramuscularly sarin,and when the mean blood pressure(MBP) was decreased to 40-45 mmHg,the drugs were intramuscularly injected and the changes of vascular active substances such as nitric oxide (NO),PGI₂,atrial natriuretic peptide (ANP),endothelin (ET),angiotensinⅡ(AngⅡ) and TXA₂ before and after treated 15,30 and 60 min were observed.RESULTS: In anesthetized dogs intoxicated with cholinesterase inhibitor sarin,the plasma vascular active substances NO,PGI₂,ANP,ET,AngⅡand TXA₂ were increased significantly.After treated with mecamylamine and atropine 15 min,all the six vascular active substances were decreased markedly.After treated 60 min,they were almost resumed to the normal levels.The therapeutic effects of combination of mecamylamine and atropine were much better than those of mecamylamine or atropine used separately.CONCLUSION: The levels of vascular active substances NO,PGI₂,ANP,ET,AngⅡand TXA₂ in plasma can reflect the severity of circulation failure.There were synergic effects between mecamylamine and atropine against circulation failures induced by sarin.

Key words: cholinesterase inhibitor, sarin, circulatory failure, mecamylamine, vascular active substances

中图分类号:

R965

龙超良, 王汝欢, 张雁芳, 李军, 汪海. 胆碱酯酶抑制剂沙林诱发犬循环衰竭时血液内心血管活性物质的变化以及抗毒剂的对抗效应[J]. 中国临床药理学与治疗学, 2006, 11(3): 266-269.

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