抑制肠道细菌丛和非特异性羧酸酯酶对T2毒素在原位灌流大鼠小肠袢中代谢的影响  

Effect of inhibiting intestinal microflora and nonspecific carboxylesterase on the metabolism of T2 toxin in the in situ perfused rat small intestinal loop

作　　者：李桦[1] 阮金秀[1] 杨进生[1] 

机构地区：[1]北京军事医学科学院毒物药物研究所

出　　处：《中国药理学与毒理学杂志》1994年第4期289-292,共4页Chinese Journal of Pharmacology and Toxicology

摘　　要：预先用新霉素和头孢氨苄抑制肠道细菌丛后，Ｔ２毒素在灌流小肠袢内的代谢速度明显减慢，ｔ１／２β由正常的２６ｍｉｎ延长为１３１ｍｉｎ．主要代谢产物ＨＴ２的生成减少．Ｔ２毒素羟化生成３′－羟基ＨＴ２的反应被抑制．当Ｔ２毒素对预先用二异丙基氟磷酸酯抑制酯酶的小肠袢进行肠系膜一门脉血管灌流时．Ｔ２毒素的ｔ１／２β由正常的４７ｍｉｎ延长至１２０ｍｉｎ，ＨＴ２的生成部分被抑制，而３′－ＯＨＨＴ２的生成量显著增加．同时抑制肠道细菌丛和酯酶．Ｔ２毒素在小肠中的代谢转化基本被阻断．实验结果表明，Ｔ２毒素在大鼠小肠中的代谢转化反应主要在肠道细菌丛酶系统和非特异性羧酸酯酶的共同作用下进行．抑制肠道细菌丛酶系统可同时减少Ｔ２毒素在小肠中的水解和羟化反应．而抑制酯酶仅能减少水解反应．与此同时轻化产物增加．The effect of inhibiting intestinal microflora and nonspecific carboxylesterase(NCBE)onthe melabolism of T2 toXin in rat intestine was investi-gated by using the in situ perfused rat small intestinalloop. After the intestinal microflora was reduced bytreating rats previously wilh an antibiotic mixture ofneomycin(Neo) and cefalexin(Cef),the metabolic rateof T2 toxin was markedly decrcased and the amount ofthe toxin absorbed into the perfusate was increased.Theelimination half-life of the toxin in the perfusate was ex-tended from 26 min of the normal group to 131 min ofthe group treated with Neo and Cef. Both formationrate and amount of the major product HT2 in theintestinal loop Were decreased.Another metabolic path.way in which T2 toxin Was hydroxylated to 3'OHHT2was blocked.When T2 toxin was vascularly perfusedthrough the mesenteric artery-portal vein of the rat intes-tine pretreated with NCBE inhibitor,diisopropylfluorophosphate(DFP), the elimination rate of the toxin fromnerfusate also slowed down.The half-life of the toxinwas changed from 47 min of the normal group to 120min of the pretreated group. The formation of HT2 waspartly inhibited. On the contrary, the fonnation of3'-OHHT2 was markedly increased. While the rat intes-line was pretreated with both antibiotics and DFPsimultaneously,the biotransformation of T2 toxin inthe intestine was almost blocked and the toxin was ab-sorbed into the perfusate with the absorption half-lifeof 41 min. From the present results it is concluded thatthe biotransformation of T2 toxin in the in situ pe-rfused rat small intestine is catalyzed by the intestinalmicroflora enzyme system and NCBE. Inhihtion of theintestinal microflora may reduce both hydrolysis andhydroxylation of T2 toxin,but the esterase inhibitor canreduce the hydrolytic pathway of the toxin and thusenhance the hydroxylation reaction product.

关 键 词：T2毒素 肠道细菌丛 羧酸酯水解酶 小肠 

分 类 号：R963[医药卫生—微生物与生化药学] R978.1[医药卫生—药理学]