小鼠光气染毒对肺脏细胞的凋亡作用

背景与目的:小鼠原代肺Ⅱ型细胞的分离、培养方法的建立,探讨光气对肺水肿小鼠的肺脏细胞凋亡的诱导作用.材料与方法:12只二级BALB/c小鼠,雄性,随机分为2组:正常对照组(6只)和染毒组(6只).正常对照组小鼠以空气为对照,染毒组小鼠给予11.9 mg/L剂量的光气,时间为5 min.染毒后4 h,分离、培养肺Ⅱ型细胞,电镜观察两组小鼠肺Ⅱ型细胞、肺Ⅰ型细胞、嗜酸性粒细胞、巨噬细胞、淋巴细胞和纤毛细胞凋亡情况.结果:单宁酸染色和电镜鉴定培养细胞为小鼠原代肺Ⅱ型细胞;小鼠给予11.9 mg/L的光气染毒5 min,电镜显示光气染毒肺水肿小鼠原代肺Ⅱ型细胞出现凋亡小体,肺Ⅱ型细胞核染色质呈现月牙型,嗜酸性粒细胞、巨噬细胞、淋巴细胞和纤毛细胞均出现凋亡征象.结论:建立了小鼠原代肺Ⅱ型细胞的分离、培养方法,证明光气染毒可造成肺水肿小鼠肺脏细胞发生凋亡.     

光气染毒造成小鼠肺脏的氧化损伤

目的　研究小鼠光气染毒后不同时间对肺脏的氧化损伤作用。方法　 4 0只雄性小鼠 ,随机分为 4组。正常对照组小鼠以空气为对照 ,染毒组小鼠给予 11.9mg/L剂量的光气 ,时间为5min ,分别染毒后 2h、4h、8h ,测定各组小鼠肺脏的湿干比和肺匀浆液的丙二醛 (MDA)含量、总超氧化物歧化酶 (T SOD)活力、还原型谷胱甘肽 (GSH)含量。结果　随着光气染毒时间的增加 ,小鼠肺脏的湿干比显著增加 (P <0 .0 5 ) ;染毒后 4h ,肺组织MDA含量和T SOD活力显著升高(P <0 .0 5 ) ,GSH含量在染毒后 2h显著降低 (P <0 .0 5 )。结论　光气染毒可引起小鼠肺水肿和肺脏氧化损伤。     

光气吸入对大鼠肺组织基因表达谱的影响

目的:研究光气吸入染毒前后大鼠肺组织基因表达的差异,探讨光气肺损伤作用相关的基因谱.方法:提取正常对照组和光气染毒组肺组织的总RNA,并以此为模板制备荧光标记的cRNA靶物,经杂交、洗涤后,通过扫描荧光强度和计算机软件分析,寻找染毒前后上调和下调的差异表达基因.结果:在大鼠20500个靶基因中,初步筛选出801条差异表达基因,表达上调的有557条,下调的有254条.根据基因的生物学功能,差异表达基因被分为9类:G1自由基\电子传递相关;G2应激炎症相关;G3物质代谢相关;G4细胞增殖\分化\凋亡相关;G5基因表达调控相关;G6受体和信号转导相关;G7蛋白质修饰\分解相关;G8细胞骨架\运动相关;G9离子通道与物质转运相关等.结论:光气可以引起肺组织基因的多发性改变,其差异表达基因的功能分类为进一步探讨光气中毒发生、发展的机制和有效救治提供新的线索和思路.     

Possible immediate and long-term health effects following exposure to chemical warfare agents

Agents of chemical warfare continue to pose a threat to human life. Organophosphorus compounds are possibly the best known and most used agents in recent times. These are known to produce acute ill health and death and, probably equally important, many diverse delayed effects, many of which are not clinically nor pathologically well defined. The immediate and delayed effects of organophosphorus compounds, in particular, and those of other known agents of chemical warfare, such as mustard gas, Lewisite, phosgene, cyanides and the newer crowd control agents, are reviewed. Environmental sequelae of these agents are gaining importance as probable causes of chronic ill health amongst those living in regions where these agents have been used. The need to study the pattern of disease in exposed populations is emphasised.     

肺损伤性毒剂的实验研究进展

肺损伤性毒剂,也称肺刺激剂和窒息性毒剂,作用靶器官主要是肺,可引起潜在持久的呼吸抑制,并可迅速发展为急性肺损伤(ALI)、肺水肿,严重者将导致死亡.近年来,随着对其作用机制研究的深入,开展了不少针对性的实验研究,并取得了一定的进展.本文从肺损伤性毒剂研究概况、致病机制、生物标志物等3个方面综述了近年来肺损伤性毒剂实验研究的相关进展,为推动中毒性ALI的预防、诊断和临床治疗提供参考借鉴.     

高氧液体对兔窒息性中毒肺水肿指标的影响

目的　观察兔光气染毒后肺水肿指标及肺泡灌洗液成分的变化 ,并进一步探讨高氧液对光气中毒性损伤的保护作用。方法　 18只新西兰大白兔随机均分为正常对照组、平衡盐组 (光气中毒后输注平衡盐 30ml·kg-1)和高氧液组(光气中毒后输注高氧液 30ml·kg-1) ,各组动物均于实验开始后 8h处死 ,立即开胸取肺 ,称取全肺湿重和右肺湿重 ,测定肺湿干比 (W/D)、肺水含量 (LW)和肺系数 (L/B) ;左肺用 37℃生理盐水进行灌洗 ,每次 5ml,共 3次 ,总回收率达 90 %以上 ,测定支气管肺泡灌洗液 (BALF)中丙二醛 (MDA)含量、谷胱甘肽过氧化物酶(GSH Px)活性及蛋白含量。结果　与正常对照组比较 ,高氧液组、平衡盐组的肺水肿指标及BALF中MDA、蛋白含量均显著升高 (P <0 0 5或P <0 0 1) ,GSH Px活力明显下降 (P <0 0 5或P <0 0 1)。与平衡盐组比较 ,高氧液组GSH Px活力明显增高 (P <0 0 1) ,BALF中MDA、蛋白含量均显著下降 (P <0 0 5或P <0 0 1) ,W/D、LW和L/B明显降低 (P <0 0 5 )。结论　脂质过氧化参与了光气中毒性肺损伤的发病 ,静脉输注高氧液对光气中毒肺损伤有一定的保护作用     

维生素E与硫辛酸对光气损伤的抗氧化作用探讨

背景与目的:观察维生素E或/和硫辛酸对光气损伤小鼠的抗氧化作用,为临床救治光气中毒提供实验资料.材料与方法:确定小鼠在光气中毒后体内发生了一定程度的氧化损伤,然后分组给予维生素E或/和硫辛酸,应用全自动血球分析仪进行血液学分析,采用荧光法测定动物肝脏与肺脏MDA.结果:维生素E(6 mg/kg)或/和硫辛酸(0.8 mg/kg)对光气引起的全血WBC、PLT降低有促进恢复作用,对肝脏与肺脏MDA的升高有一定的抑制作用,维生素E单用组效果显著,维生素E与硫辛酸复合组效果最差.结论:维生素E对光气导致的脂质过氧化的抗氧化作用优于硫辛酸,维生素E与硫辛酸复合组效果不及单用.     

Phosgene (chlorophenyl)hydrazones, strong sensitizers found in yellow sweaters bleached with sodium hypochlorite, defined as causative allergens for contact dermatitis by an experimental screening method in animals

12 young men developed allergic contact dermatitis from wearing yellow cotton sweaters. We attempted to identify the causative agents by an experimental screening method in animals. Guinea pigs were sensitized with an acetone extract of the sweater material, by means of the guinea pig maximization test (GPMT). Active ingredients were then separated from the extract, by step-by-step patch test screening of chromatographic fractions in the guinea pigs, and finally analyzed by gas chromatography-mass spectrometry (GC-MS). Although there were 2 allergens with important activity (1 in the fraction eluted from the silica gel column with hexane, and 1 in the methanol fraction), the present study is focussed on the fat-soluble allergens in the hexane fraction. GC-MS analysis revealed that 4 kinds of phosgene (chlorophenyl)hydrazones (PCPHs) were present in the hexane fraction. PCPHs prepared in our laboratory showed strong eliciting activities, not only in the guinea pigs sensitized with the extract, but also in a male volunteer sensitized by exposure to a yellow sweater during irritancy testing. Phosgene (2,5-dichlorophenyl)hydrazone, which was the main component among the PCPHs found in the sweater, sensitized guinea pigs even at the 1 ppm level. From these results, we conclude that PCPHs were one of the allergens responsible for the cases.