宾赛克嗪预防胆碱酯酶抑制剂中毒呼吸衰竭的实验研究  

Experimental study on preventive effects of benthiactzine against respiratory failure induced by cholinesterase inhibitor in rats

作　　者：莫晨[1,2] 龙超良[1] 王汝欢[1,3] 汪海[1,3] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]武警总医院干部病房二科,北京100039 [3]北京赛德维康医药研究院,北京100039

出　　处：《中国临床药理学与治疗学》2010年第2期135-139,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家重大新药创制科技重大专项(2009ZXJ09002-014)

摘　　要：目的:制作胆碱酯酶抑制剂敌敌畏中毒所致呼吸衰竭的实验动物模型,评价宾赛克嗪预防敌敌畏中毒呼吸衰竭的效果。方法:健康Wistar雄性大鼠40只,随机分为4组:模型组、宾赛克嗪0.5 mg/kg预防用药组、1.0 mg/kg预防用药组及2.0 mg/kg预防用药组,每组10只。预防用药后半小时一次性敌敌畏(2,2-二氯乙烯基二甲基磷酸酯,DDVP)腹腔注射染毒,观察出现呼吸衰竭的时间及各组的症状、呼吸频率的改变、动脉血气分析+离子分析的变化及肺组织病理学改变。结果:DDVP染毒后,中毒对照组动物均出现肌颤、躁动、口鼻大量分泌物、肌无力症状,直至口唇及四肢紫绀、呼吸困难、惊厥,均于3～5 min内死亡。宾赛克嗪预防给药各组动物仅出现肌颤、躁动、肌无力等轻度N样症状,均逐渐自行缓解,观察至2 h均未出现紫绀、呼吸困难、惊厥等表现。宾赛克嗪预防各组染毒前、染毒后5 min及染毒后半小时3个时点血气分析和离子分析的结果均无统计学差异。中毒死亡组动物肺组织HE染色可见肺泡间隔增厚,肺泡壁毛细血管壁充血、灶状出血,伴炎性细胞浸润,少量肺泡水肿。宾赛克嗪预防各组动物肺组织结构均大致正常。结论:新型抗毒剂宾赛克嗪能够有效预防有机磷农药敌敌畏中毒呼吸衰竭的发生。AIM： To investigate the preven tive effects of benthiactzine against respiratory failure induced by cholinesterase inhibitor DDVP in rats. METHODS： 40 healthy Wistar male rats were divided into 4 groups randomly： poisoning group, benthiactzine 0.5, 1.0 and 2.0 mg/kg preventive groups. Rats were poisoned with DDVP （i. p. ） for 30 min after benthiactzine was injected beforehand. The symptoms, respiratory rate, blood gas analysis and the pathological change were observed. RESULTS： After DDVP poisoning, the rats of poisoning group all died within 3-5 min with the symptoms of fasciculation, cyanosis and convulsion et al. The rats of benthiactzine preventive groups showed mild N symptoms such as fasciculation and weakness, and then recovered. The blood gas analysis demonstrated no damages caused by the poison. The lung tissue slides of poisoning group with HE staining showed that the pulmonary vessels were dilated and filled with erythrocytes, pulmonary intervals became wide and red blood cells could be seen in alveolar and bronchial cavities, and many inflammatory cells accumulated, pulmonary edema and hemorrhage appeared. The lung tissues of rats in preventive groups were normal. CONCLUSION.. Benthiactzine can effectively prevent respiratory failure induced by DDVP.

关 键 词：宾赛克嗪 胆碱酯酶抑制剂 有机磷农药 敌敌畏 呼吸衰竭 

分 类 号：R965[医药卫生—药理学]