卡托普利对大鼠全氟异丁烯急性吸入性肺损伤的保护作用研究  

Protective effect of captopril against rats′ acute lung injury induced by perfluoroisobutylene inhalation

作　　者：李宝宝 许兴兴 赵建 丁日高 王永安 LI Bao-bao;XU Xing-xing;ZHA Jian;DING Ri-gao;WANG Yong-an(State Key Laboratory of Highly Toxic Substances for Anti-Drug Research,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China;General Hospital of Eastern Theater Command,PLA,Nanjing 210002,China)

机构地区：[1]军事科学院军事医学研究院毒物药物研究所,抗毒药物与毒理学国家重点实验室,北京100850 [2]解放军东部战区总医院,南京210002

出　　处：《军事医学》2022年第2期127-131,共5页Military Medical Sciences

摘　　要：目的 探讨卡托普利对全氟异丁烯(PFIB)急性吸入性肺损伤的保护作用及其机制。方法 采用实验室自制的全身暴露动态染毒系统对实验大鼠进行吸入染毒。48只雄性Wistar大鼠随机分为正常对照组、卡托普利药物对照组、PFIB染毒对照组和PFIB染毒+低、中、高剂量卡托普利治疗组(n=8)。其中PFIB染毒各组染毒剂量为260 mg/m^(3)×5 min,正常对照组和卡托普利药物对照组于过滤空气中暴露5 min。卡托普利低、中、高各组给药剂量分别为31.5、63和126 mg/kg,染毒后15 min及3、6、9 h分别腹腔注射给药1次;卡托普利药物对照组于相同时间点腹腔注射卡托普利剂量为126 mg/kg;正常对照组、PFIB染毒对照组于相同时间点腹腔注射相应体积的生理盐水。记录各组大鼠染毒后24 h存活数,制备支气管肺泡灌洗液(BALF),留存肺组织样本,测定肺系数、BALF中蛋白和磷脂含量,以及肺组织匀浆中脂质过氧化物(LPO)含量,制备肺组织病理切片并进行组织病理学检查。结果 与正常对照组相比,PFIB染毒后24 h大鼠各项肺系数、BALF中蛋白及磷脂含量、肺组织匀浆中LPO含量均显著升高(P<0.05),卡托普利治疗后,PFIB染毒+低、中、高剂量卡托普利各组肺系数、BALF中蛋白及磷脂含量、肺组织匀浆中LPO含量均显著降低(P<0.05),卡托普利药物对照组未见明显改变。组织病理学结果显示,卡托普利治疗后各组大鼠肺损伤程度明显缓解,且具有剂量依赖性。结论 卡托普利治疗可明显改善PFIB吸入性急性肺损伤,其作用机制可能与其对氧化还原系统的保护作用有关。Objective To explore the protective effect and mechanism of captopril against acute lung injury induced by perfluoroisobutylene(PFIB)inhalation. Methods A general-exposed dynamic contamination system designed by our own laboratory was used to have the rats suck the toxicant. The rats were body-exposed to the toxic environment in the dynamic toxic gas-absorbed equipment. Forty-eight male Wistar rats were randomly divided into 6 groups:the normal control group,captopril control group,PFIB-exposure control group,PFIB-exposure + low-dose captopril treatment group,PFIB-exposure +middle-dose captopril treatment group and PFIB-exposure + high-dose captopril treatment group(n=8). The concentration of PFIB exposure was 260 mg/m^(3) and the exposure duration was 5 minutes. The normal control group and captopril control group were exposed to filtered air for 5 minutes. The dosages of captopril for low-,middle-and high-dose groups were 31.5,63 and 126 mg/kg respectivly and the rats were injected with captopril 15 minutes,and 3,6,9 hours post PFIB exposure respectively. Rats in the captopril control group were intraperitoneally injected with 126 mg/kg captopril,and the balnk control group and the PFIB-exposure control group with the same volume of normal saline at the same time. 24 hours after PFIB exposure,the survival numbers of rats were recorded. The bronchoalveolar lavage fluid(BALF)and lung tissue of living rats were collected,the lung coefficient,protein concentration and phospholipid concentration of BALF and the lipid peroxidase content of lung tissue homogenate were determined. Histopathological evaluation was performed for lung tissue. Results The lung index,protein concentration and phospholipid concentration of BALF and the lipid peroxidase content of lung tissue homogenate in the PFIB-exposure control group were obviously higher than those in the normal control group,and the difference was statistically significant(P<0.05),but there was no significant difference between the captopri control group and the normal

关 键 词：动物模型 急性肺损伤 全氟异丁烯 卡托普利 氧化还原 支气管肺泡灌洗液 

分 类 号：R563.1[医药卫生—呼吸系统]