Blood and bronchoalveolar lavage fluid acetylcholinesterase levels following microinstillation inhalation exposure to sarin in Guinea pigs.
Blood and bronchoalveolar lavage fluid acetylcholinesterase levels following microinstillation inhalation exposure to sarin in Guinea pigs.
复制标题
豚鼠微滴吸入接触沙林后血液和支气管肺泡灌洗液乙酰胆碱酯酶水平。
DOI：
10.1080/08958370802050957
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发表时间：
2008
影响因子：
2.1
通讯作者：
Nambiar,MadhusoodanaP
中科院分区：
文献类型：
--
作者：
Che,MagnusM;Conti,Michele;Boylan,Megan;Sciuto,AlfredM;Gordon,RichardK;Nambiar,MadhusoodanaP
我们测定了吸入化学威胁神经毒剂（CTNA）沙林后支气管肺泡灌洗液（BALF）中乙酰胆碱酯酶（AChE）和丁基胆碱酯酶（BChE）的抑制作用。采用微滴吸入暴露技术，将年龄和体重匹配的雄性豚鼠暴露于5种不同剂量的沙林（169.3、338.7、508、677.4和846.5 mg/m3）中4分钟。该技术包括在气管中使用微导管雾化药剂，微导管的中心孔用于输送药剂，而多个外围孔用于在尖端泵入空气使药剂雾化。接触高剂量沙林的动物偶尔会出现癫痫发作，并在接触后15分钟内死亡。微滴法测定沙林的lct50接近677.4 mg/m3。暴露后15分钟，耳血AChE活性表现出剂量依赖性抑制。在沙林暴露后35和55分钟内，血AChE的抑制保持不变，表明没有肺库效应。暴露于677.4和846.5 mg/m3沙林后24小时安乐死的存活动物的心脏血液AChE和丁酰胆碱酯酶（BChE）活性显示出剂量依赖性抑制，抑制率为60%。支气管肺泡灌洗液（BALF）中AChE和BChE活性在338.7 ~ 677.4 mg/m3沙林暴露时略有升高，但在169.3 mg/m3沙林暴露时略有抑制。相比之下，免疫印迹法检测的AChE蛋白水平在BALF中升高至169.3 mg/m3。肺损伤的生物标志物BALF蛋白水平在338.7 mg/m3时升高最大，随着沙林剂量的增加，升高幅度减小。BALF蛋白水平与AChE和BChE活性相关。这些数据表明，沙林微滴吸入暴露可导致呼吸毒性和肺损伤，其特征是灌洗液中乙酰胆碱酯酶、脑碱酯酶和蛋白质水平的变化。
We determined acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition in the bronchoalveolar lavage fluid (BALF) following inhalation exposure to chemical threat nerve agent (CTNA) sarin. Age- and weight-matched male guinea pigs were exposed to five different doses of sarin (169.3, 338.7, 508, 677.4, and 846.5 mg/m3) using a microinstillation inhalation exposure technique for 4 min. The technique involves aerosolization of the agent in the trachea using a microcatheter with a center hole that delivers the agent and multiple peripheral holes that pumps air to aerosolize the agent at the tip. Animals exposed to higher doses of sarin occasionally developed seizures and succumbed to death within 15 min after exposure. The LCt50for sarin using the microinstillation technique was determined to be close to 677.4 mg/m3. Ear blood AChE activity showed a dose-dependent inhibition at 15 min postexposure. The inhibition of blood AChE remained constant over 35 and 55 min after sarin exposure indicating that there was no lung depot effect. Cardiac blood AChE and butyrylcholinesterase (BChE) activity in surviving animals euthanized at 24 h postexposure showed a dose-dependent inhibition with an inhibition of 60% at 677.4 and 846.5 mg/m3sarin exposure. AChE and BChE activity in bronchoalveolar lavage fluid (BALF) showed a slight increase at 338.7 to 677.4 mg/m3sarin exposure but a marginal inhibition at 169.3 mg/m3. In contrast, the AChE protein levels determined by immunoblotting showed an increase at 169.3 mg/m3in the BALF. The BALF protein level, a biomarker of lung injury, was increased maximally at 338.7 mg/m3and that increase was dropped with an increase in the dose of sarin. The BALF protein levels correlated with the AChE and BChE activity. These data suggest that sarin microinstillation inhalation exposure results in respiratory toxicity and lung injury characterized by changes in lavage AChE, BChE, and protein levels.