Page 77 - 《中国药房》2021年第1期

Comparative Study of Protective Effects of Atomization Inhalation and Intraperitoneal Injection of
Edaravone on Smoke Inhalation Lung Injury Model Rats
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XIAO Changshuan ，LIU Yaping ，YANG Jingzhe（1. Dept. of Burn and Plastic Surgery，the Affiliated Hospital
of Chengde Medical University，Hebei Chengde 067000，China；2. Dept. Two of Gynaecology，the Affiliated
Hospital of Chengde Medical University，Hebei Chengde 067000，China）

ABSTRACT OBJECTIVE：To compare the protective effect of atomization inhalation and intraperitoneal injection of edaravone
on acute lung injury in smoke inhalation lung injury model rats. METHODS：Thirty male SD rats were divided into normal control
group（group A），injury group（group B），intraperitoneal injection group（group C），low-dose aerosol inhalation group（group
D），high-dose aerosol inhalation group（group E）according to random numble table，with 6 rats in each group. Group B-E were
placed in smoke generator containing pine sawdust to induce smoke inhalation lung injury model. In group A，the operation was the
same as above except that the pine sawdust was not placed. Thirty minutes after modeling，group C were injected intraperitoneally
with edaravone 18 mg/kg（every 70 min，4 times in total）. Group D and E inhaled edaravone 9，1.8 mg/kg（every 60 min，lasting
for 10 min each time，4 times in total）. The rats were treated by no means in group A and group B. Six hours after last
medication，arterial blood gas analysis was performed，and the lung wet to dry ratio（W/D）and water content of lung tissue were
calculated. The levels of TNF-α，IL-6 and IL-10 in serum were detected by double antibody ELISA. The contents of MDA，MPO，
SOD and Caspase-3 in lung tissue were determined by ELISA and other methods. HE staining was used to observe the pathological
changes of lung tissue. The apoptotic rate of cells in lung tissue were determined by TUNEL assay. RESULTS：No abnormality was
found in lung tissue of group A；in group B，hemorrhage and edema were found in lung tissue，alveolar structure was difficult to
identify，and inflammatory cells and red blood cell infiltration were seen. Above symptoms of rats in group C-E were improved to
different extent. Compared with group A，PaO2/FiO2 and SOD content of lung tissue were decreased significantly in other groups
（P＜0.05）；water content of lung tissue，W/D，serum contents of TNF-α ，IL-6 and IL-10，the contents of MDA，MPO and
Caspase-3 in lung tissue，apoptotic rate were increased significantly（P＜0.05）. Compared with group B，PaO2/FiO2 and serum
contents of IL-10 were increased significantly in administration groups （P＜0.05）；water content of lung tissue，W/D，serum
contents of TNF-α and IL-6，the contents of MDA，MPO and Caspase-3 in lung tissue，apoptotic rate were significantly
decreased，in dose-dependent manner（P＜0.05）. CONCLUSIONS：Edaravone has a certain protective effect on smoke inhalation
lung injury model rat. It can reduce the production and release of inflammatory mediators and/or cytokines，reduce the peroxide
damage and inhibit cell apoptosis in a dose-dependent manner. The effect of atomization inhalation is more obvious than that of
intraperitoneal injection.
KEYWORDS Atomization inhalation； Intraperitoneal injection； Edaravone； Smoke inhalation lung injury； Dose-effect
relationship；Rats；Protective effect；Inflammation factor

近年来有数据显示，各种火灾事故所致死亡的人员 症反应及继发性损害成为当前研究的热点之一。目前，
[1]
中，有 75％被证实合并不同程度的吸入性损伤 。吸入 多种抗炎及抗氧化剂被广泛应用于动物研究和临床治
性损伤是发生在呼吸道及肺实质、因热力和（或）烟雾造 疗中，其中依达拉奉是近年来较为常见的一种新型氧自
成的一种烧伤严重合并症，具有病情危重、发病隐匿等 由基清除剂。研究表明，该药可通过抑制脂质过氧化及
特点 。研究表明，吸入性肺损伤发病机制较复杂，可能 调节炎症因子分泌、抑制细胞凋亡等途径来发挥神经系
[1]
与热力/烟雾等致伤因素激活肺部炎症细胞后分泌某些 统保护作用 。多项研究表明，依达拉奉在多种原因导
[4]
炎症介质及细胞因子，导致失控性炎症反应发生，产生 致的急性肺损伤中均显示出积极的作用 [5-6] ，但将该药用
大量氧自由基，继而启动系统性炎症反应综合征（SIRS） 于改善烟雾吸入性肺损伤，目前国内外报道较少。此
有关，严重时可引发呼吸窘迫综合征（ARDS）以及多器 外，依达拉奉具有较好的亲脂性，且分子量小，故能较容
官功能障碍综合征（MODF），严重危害人体健康 。对 易地透过细胞膜渗入局部组织器官及动静脉并获得良
[2]
于吸入性肺损伤，临床现多采用气管切开及灌洗、机械 好的组织及血管内药物浓度 ，加之雾化吸入方式可使
[7]
通气等介入综合治疗措施，但多因治疗费用昂贵、收效 药物直达靶器官，因此笔者推测给药方式的改变可能更
甚微而被人们诟病；此外，国内外学者还进行了相关药 有利于肺保护。基于此，本研究拟通过早期雾化吸入不
物的体内研究，但其安全性及有效性欠佳 。因此，寻找 同剂量及腹腔注射高剂量依达拉奉对烟雾吸入性肺损
[3]
可靠的干预手段以有效减轻吸入性肺损伤的原发性炎 伤模型大鼠进行干预，比较两种给药方式对烟雾吸入性

中国药房 2021年第32卷第1期 China Pharmacy 2021 Vol. 32 No. 1 ·71 ·