胆碱酯酶抑制剂中毒大鼠肠屏障功能和形态结构变化及宾赛克嗪治疗作用的研究  

Functional and morphological structure changes in the gut barrier during cholinesterase inhibitor intoxication and therapeutic effect of benthiactzine in rats

作　　者：潘志远[1] 龙超良[1] 汪海[1,2,3] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]北京赛德维康医药研究院,100039 [3]军事医学科学院卫生学环境医学研究所,天津300050

出　　处：《中国危重病急救医学》2010年第4期197-200,I0001,共5页Chinese Critical Care Medicine

摘　　要：目的观察胆碱酯酶抑制剂类神经性毒剂中毒后大鼠肠屏障功能和组织形态结构的变化以及宾赛克嗪的治疗作用。方法40只雄性Wistar大鼠按随机数字表法均分为对照组、维埃克斯染毒模型组及宾赛克嗪1、3、9mg／kg治疗组。皮下注射维埃克斯13μg／kg染毒；宾赛克嗪组在染毒后5min腹腔注射相应剂量药物。各组于染毒后3h取血，检测血浆D-乳酸浓度及二胺氧化酶（DAO）活性；同时取小肠组织，观察肠黏膜形态和超微结构变化。结果与对照组比较，模型组血浆D-乳酸浓度和DAO活性均明显升高[D-乳酸：（87．752±22．906）mg／L比（29．072±6．546）mg／L，DAO：（6．72土0．93）U／L比（2．99±0．43）U／L，均P〈O．013；宾赛克嗪1、3、9mg／kg组呈现剂量依赖性降低血浆D-乳酸浓度和DAO活性，其中宾赛克嗪9mg／kg组可逆转染毒后血浆D-乳酸浓度[（45．290±11．141）mg／L]和DA0活性[（3．17土0．68）U／L]增高（均P〈o．01）。光镜下观察模型组大鼠空肠和回肠肠壁变薄，皱壁变短，结构紊乱，固有层毛细血管扩张充血，黏膜间质水肿等病理变化；电镜下观察模型组大鼠回肠上皮细胞发生坏死，细胞器损伤，紧密连接破坏等变化。宾赛克嗪1、3、9mg／kg组呈现剂量依赖性抑制小肠的病理变化。结论胆碱酯酶抑制剂中毒时出现肠黏膜上皮细胞损伤，肠黏膜屏障功能破坏，通透性增加；宾赛克嗪能抑制中毒肠黏膜屏障结构和功能的损伤。Objective To investigate the functional and morphological structure changes in the gut barrier of rats induced by cholinesterase inhibitor VX poisoning, and the therapeutic effect of benthiactzine. Methods Forty male Wistar rats were randomly divided into five groups., normal saline control group, VX poisoning （model） group, benthiactzine 1, 3, 9 mg/kg treatment groups, with 8 rats in each group. In the benthiactzine treatment groups, different dosages of the drug were respectively given （intraperitoneal injection） 5 minutes after VX poisoning （13 μg/kg subcutaneous injection）. The plasma concentration of D-lactate and the diamine oxidase （DAO） activity, which reflected the gut barrier function, were measured at 3 hours after VX poisoning. At the same time point, the specimens from jejunum and ileum were harvested. The morphological changes in the intestinal mucosa were determined with light microscope and electron microscope. Results After VX poisoning, the plasma D-lactate concentration and the DAO activity in model group were significantly increased compared with those of control group [D-lactate concentration in model group was （87. 752± 22. 906） mg/L which was higher than that of control group （29. 072±6. 546） mg/L; DAO activity in model group was （6.72±0.93） U/L which was higher than that of control group （2.99±0.43） U/L, both P〈0.01]. These values could be decreased dose-dependently after benthiactzine 1, 3, 9 mg/kg administration after the VX poisoning. Furthermore, the increase in D-lactate （45. 290±11. 141） mg/L and DAO activity （3.17±0.68） U/L could be totally reversed by 9 mg/kg of benthiactzine （both P〈0.01）. In model group, the intestinal mucosal epithelial injury was obvious at 3 hours after VX poisoning as shown under light microscope, including diminution of the mucosal thickness and the height of villi in jejunum and ileum, interstitial edema, angiotelectasis. Also electronic microscopic examination revealed damaged organelles and cell tight

关 键 词：胆碱酯酶抑制剂 宾赛克嗪 二胺氧化酶 D-乳酸 肠屏障功能 

分 类 号：R595.4[医药卫生—内科学]