GSH和NEC合剂对光气染毒小鼠肺水肿的防治作用

Prevention Effect of GSH and NEC on Pulmonary Edema in Mice Induced by Phosgene Exposure

目的探讨光气肺水肿形成机理及还原型谷胱甘肽(GSH)、N-乙酰半胱氨酸(NEC)混合溶液对小鼠光气染毒所致肺水肿的影响。方法30只昆明小鼠被随机分为正常组、染毒组和给药组。染毒组与给药组在光气染毒1min后,分别腹腔注射5ml生理盐水和GSH、NEC混合溶液(GSH:4mg/ml,NEC:2mg/ml)。正常组在假染毒1min后,腹腔注射生理盐水5ml。2h后处死小鼠,取肺脏测湿干比,取肝脏测一氧化氮(NO)含量(μmol.gprot-1)、一氧化氮合酶(NOS)活性(U.mgprot-1)及总抗氧化力(T-AOC)。结果正常组的肺湿干比为4.441±0.829、肝脏NO含量为0.462±0.302、NOS活力为0.745±0.516,总抗氧化力为0.1620±0.7937。与正常组相比,染毒组肺湿干比(6.897±1.881)、肝脏NO含量(1.774±1.485)、NOS活力(4.506±3.617)以及总抗氧化力(0.3607±0.1784)均显著升高(P>0.05)。与染毒组相比,给药组的肺湿干比(4.931±1.546)、肝NOS活力(1.234±0.663)以及总抗氧化力(0.2066±0.1074)显著性降低,肝脏NO含量(0.860±0.822)有所降低,但差异无统计学意义(P>0.05)。结论光气中毒引起的肺水肿可能与光气对肺脏的氧化损伤有关;GSH与NEC的混合液对光气引起的氧化损伤有保护作用,可以降低肺湿干比、肝脏NO含量、NOS活力以及总抗氧化力,对光气急性吸入所致的肺水肿有一定的治疗效果。

Objective To investigate the mechanism of pulmonary edema induced by phosgene poisoning and to probe into possible curative effect of combination of reduced glutathione （GSH） and N-acetylcysteine （ NEC ） on phosgene poisoning. Methods A total of 30 mice were divided randomly into three groups： control group, poisoned group and treatment group. Poisoned group and treatment group were exposed to phosgene for 1 min, and then intraperitoneal injected with saline and GSH ＋ NEC solution（GSH： 4 mg/ml, NEC： 2 mg/ml）respectively. Animals in control group were not exposed to phosgene but injected with 5 ml saline. All animals were sacrificed 2 hours later, and the wet weight to dried weight （WW/DW） of lung and NO （μmg ·g prot^- 1）, NOS （U·mg prot^- 1） and T-AOC （ U·mg prot^- 1 ） levels of liver were examined. Results In control group, the WW/DW of lung was 4.441±0. 829, the content of NO was 0. 462 ±0. 302, the activity of NOS was 0. 745 ±0. 516, and the level of T-AOC was 0. 162 0±0. 793 7. Compared with control group, WW/DW of the lung（6. 897 ± 1. 881 ）, the content of NO（ 1.774± 1.485）, the activity of NOS（4.506 ±3. 617） , and the level of T-AOC（ 0. 360 7 ±0. 178 4） in the poisoned group, all increased significantly （P 〈0. 05）. Meanwhile, compared with poisoned group, animals in treatment group showed significant decrease （ P 〈 0.05 ） in their lung WW/DW （4. 931± 1. 546）, activity of liver NOS （ 1. 234 ±0. 663） and level of T-AOC （0. 206 6 ±0. 107 4） ; the content of liver NO also decreased but not significantly （0.05 〈 P 〈 0. 1 ）. Conclusion Phosgene related pul- monary edema might be a result of oxidative damage of the lung. Injection of GSH ＋ NEC solution to compensate for the loss of anti-oxidative substance can mitigate the pulmonary damage induced by phosgene.