化学中毒与急性缺氧的双因素联合效应的实验研究  

Study on the two-factor combined effect of chemical intoxication and acute hypoxia

作　　者：董兆君[1] 吴强[1] 赵吉清[1] 林海[1] 蔡颖[1] 刘勇[1] 李云鹏[1] 袁菊芳[1] 王仕丽[1] 杨书 恽榴红[3] 阮金秀[3] 

机构地区：[1]第三军医大学预防医学系军事毒理学教研室,重庆400038 [2]第三军医大学成都军医学院军事预防医学教研室,成都610083 [3]军事医学科学院,北京100850

出　　处：《第三军医大学学报》2003年第12期1029-1033,共5页Journal of Third Military Medical University

基　　金：全军"九五"重点课题资助项目 ( 96L0 15)

摘　　要：目的　研究化学中毒与急性缺氧两因素的联合效应。方法　建立常压常氧、常压缺氧和低压缺氧 3种模型 ,以梭曼 (Soman)、氰化钠 (NaCN)和 4 DMAP ( 4 dimethylaminophenol)为代表 ,测定大鼠、小鼠、家猫、PC1 2 细胞、兔血红细胞等在3种模型条件下对毒物药物的行为、生化和生理指标变化。结果　梭曼单独作用可导致动物协调运动下降、脑等组织含水率增加、脑组织AChE活性降低、MR下调、NE和cAMP含量增加。急性缺氧单独作用也可引起动物协调运动及自主活动的降低、脑等组织含水率的增加、外周血和脑组织AChE活性升高、MR受体上调、NE和cAMP含量增加、4 DMAP药效升高。化学中毒与急性缺氧同时作用 ,上述变化更加复杂。结论　化学中毒与急性缺氧两种因素同时作用于机体 ,对机体产生广泛而复杂的损伤作用。此种作用为两因素的联合效应。缺氧引起的机体功能下降对联合效应的增加部分贡献较大。急性缺氧既可使重要的组织成分发生质或量的变化 ,也会影响某些抗毒剂的作用强度。Objective To investigate the two factor combined effect of chemical intoxication and acute hypoxia. Methods Normobaric control, normobaric hypoxia and hypobaric hypoxia models were established for the identification of different responses of behaviors, physiological and biochemical parameters in animals and cell lines to the acute chemical impact or/and the acute hypoxia. Two kinds of high toxic compounds and one kind of antidote were representatively measured: the organophosphate soman, the cytochrome oxidase inhibitor sodium cyanide (NaCN) and the anti cyanide drug 4 dimethylaminlphenol (4 DMAP). Results Significant decreases of animal coordinate movement, brain AChE activity and muscarinic receptor (MR) Bmax were found in animals of soman intoxication under normobaric control condition. Higher brain water rate and concentrations of NE and cAMP were also confirmed after soman injection. In the animals treated with hypobaric hypoxia only, coordinate movement and locomotor activity decreased. Water rate, concentrations of NE and cAMP, AChE activity and MR Bmax in brain tissues increased. The MHb concentration in rabbit erythrocytes significantly increased by both normobaric and hypobaric hypoxia treatments. More complicated changes of the above mentioned parameters including JAKs/STATs signal transduction system were demonstrated in the animals or cells under the conditions of combined effect of soman intoxication and hypoxia. Conclusion The simultaneity of chemical intoxication and acute hypoxia can result in a combined effect in animals or cells. Hypoxia induced biochemical or physiologic abnormalities may contribute to the exacerbation of the combined injuries. Hypoxia can lead to qualitative or quantitative alterations of toxicity associated biochemical components in tissues and remodel the antidote efficacy.

关 键 词：缺氧 梭曼 4-DNAP 

分 类 号：R595[医药卫生—内科学] R827.172[医药卫生—临床医学]