摘要
目的探讨N-乙酰半胱氨酸（N-acetylcysteine，NAC）对全氟异丁烯（periluoroisobutylene,PFIB）吸入性肺损伤的保护作用及其机制。方法用自制的气体吸入染毒装置分别对小鼠和大鼠进行口鼻吸入染毒。将48只雄性ICR小鼠随机分为PFIB染毒组、NAC预防组、NAC治疗组和NAC预防＋治疗组，每组12只。PFIB染毒组除染毒外不做任何处理，NAC预防组于染毒前0．5h给药，NAC治疗组于染毒后1h给药，NAC预防＋治疗组于染毒前0．5h和染毒后1h各给药1次；给药剂量为150mg／kg，给药途径为腹腔注射。观察小鼠致死剂量PFIB（230mg／m^3，5min）染毒后的7d存活率。将18只雄性Wistar大鼠随机分为正常对照组、PFIB染毒组和NAC预防组，每组6只。对照组不做任何处理，NAC预防组于PFIB染毒前30min腹腔注射NAC（420ms／ks），PFIB染毒组于PFIB染毒前30min腹腔注射相应体积的生理盐水。在染毒后分别测定各组大鼠的呼吸功能并进行比较，评价NAC对大鼠亚致死剂量PFIB（280mg／m3×5min）所致急性肺损伤的预防作用。PFIB染毒后24h，将大鼠麻醉后进行动脉血气分析并处死，制备支气管肺泡灌洗液（bronchoalveolar lavage fluid，BALF），采集血浆和肺组织样品，测定各组大鼠的肺系数，BALF中的蛋白和磷脂含量，以及血浆和肺组织匀浆中T-SOD活力、GSH-Px活力、GSH含量的变化，蛋白免疫印迹（Western—blot）法测定大鼠肺组织中Peroxiredoxin2的表达。结果NAC预防可明显提高致死剂量PFIB染毒小鼠的存活率，治疗给药无效。与正常对照组比较，PFIB染毒组的肺系数、BALF中蛋白和磷脂含量、呼吸频率、肺组织中Peroxiredoxin2的表达显著增加，肺组织中GSH-Px的活力明显降低，差异均有统计学意义（P〈0．01）；动脉血氧分压低于正常对照组，差异有统计学意义（P〈0．05）。与PFIB染毒组比较，NAC预防组大鼠的肺系数、BALF中蛋白和磷脂含量、呼吸频率、肺组织中Peroxiredoxin2的表达明显降低，肺组织中GSH-Px活力明显增高，动脉血氧分压升高，差异均有统计学意义（P〈0．01，P〈0．05）。结论PFIB染毒吸人导致的急性肺损伤与肺部遭受刺激后发生的氧化应激相关，NAC预防能调节肺组织内氧化一还原系统，有效保护染毒动物的靶器官。
Objective To study the protective effect of N-acetylcysteine on acute lung injury induced by PFIB inhalation and its mechanism. Methods Survival experiment： 48 male ICR （CD-1） mice were randomly divided into 4 groups, i. e., PFIB control group, NAC prevention group, NAC treatment group, and NAC prevention ＋ treatment group, each group contains 12 animals. The mice of PFIB C group were exposed to PFIB without any treatment. The mice of NAC P group were exposed to PFIB 30min after NAC administration. The mice of NAC T group were exposed to PFIB lh before NAC administration, The mice of NAC P ＋T group were administrated with NAC twice （30 min before and lh after PFIB inhalation）. 150 mg/kg NAC was given by each time. The 7 days survival rate of mice after lethal dose PFIB exposure was observed. 18 male Wistar rats were randomly divided into 3 groups i.e., normal control group （N-C）, PFIB control group （PFIB-C） and NAC prevention group （NAC-P）, with each group contains 6 animals in the second experiment. The rats of N-C group received no treatment. The rats of NAC-P group and PFIB-C group were exposed to PFIB 30min after treatment of NAC （420 mg/Kg, i.p.） and saline, respectively. The respiratory functions of animals were tested before and 24 h after PFIB inhalation. The arterial blood gas was analyzed after rats were anesthetized 24 hours post sublethal dose PFIB exposure. Then samples of BALF, plasma and lung tissue were collected. Wet lung/body weight ratio, protein and phospholipid content in BALF, and T-SOD, GSH, GSH-Px in plasma and lung tissue were measured. The expression of Peroxiredoxin 2 was detected by Western-blot assay. Results NAC prevention can significantly improve the survival of mice exposed to a lethal dose PFIB while NAC treatment is ineffective. Severe lung edema was observed in rats 24 h after PFIB exposure. Compared to N-C group, the wet lung/body weight ratio, protein and phospholipid content in BALF, and respiratory rate of PFIB control group all increased significantly（P〈0.01 ）. The arterial oxygen partial pressure （PaO2） reduced significantly （P〈0.05）. The GSH-Px activity in lung tissue reduced significantly （P〈0.01） while the expression of Peroxiredoxin 2 increased significantly （P〈0.01）. NAC prophylaxis significantly reduced the wet lung/body weight ratio, protein and phospholipid content in BALF, respiratory rate of rats exposed to PFIB （P〈0.01）. Compared with PFIB-C group, the PaO2 （P〈0.05） and the activity of GSH-Px （P〈0.01） and the expression of Peroxiredoxin 2 in lung tissue （P〈0.01）were increased significantly. Conclusion Acute lung injury induced by PFIB inhalation is related to oxidative stress caused by the stimulation to lung, induced and pulmonary subjected to stimulate the generation of exposure, NAC prevention can regulation of the redox system in lung tissue and protect target organ of the treated animals effectively.
出处
《中华劳动卫生职业病杂志》
CAS
CSCD
2017年第7期481-486,共6页
Chinese Journal of Industrial Hygiene and Occupational Diseases
