雾化吸入及气管滴入阿米卡星、替加环素对健康小鼠支气管和肺组织的损伤

doi:10.6040/j.issn.1671-7554.0.2017.154

摘要/Abstract

摘要： 目的探讨雾化吸入及气管滴入阿米卡星、替加环素对健康小鼠支气管和肺组织损伤的不同。方法将144只昆明种小白鼠随机分为9组(每组16只):空白对照组、生理盐水吸入组、阿米卡星低浓度吸入组、阿米卡星高浓度吸入组、替加环素低浓度吸入组、替加环素高浓度吸入组、生理盐水滴入组、阿米卡星滴入组及替加环素滴入组,各组给予相应处理,取各组小鼠支气管和肺组织两处的病理标本,比较各组小鼠支气管和肺泡损伤程度的不同。结果替加环素高浓度吸入组及阿米卡星高浓度吸入组小鼠的肺损伤程度评分均显著高于空白对照组(P=0.001;P<0.001)。阿米卡星高浓度吸入组小鼠的肺损伤程度评分显著高于生理盐水滴入组(P<0.001),亦显著高于替加环素滴入组(P=0.001)。结论无论雾化吸入还是气管内滴入均对小鼠肺组织有损伤,而雾化吸入阿米卡星对小鼠肺泡损伤程度高于气管滴入替加环素。

关键词: 雾化吸入, 气管滴注, 阿米卡星, 替加环素, 支气管, 肺组织, 损伤

Abstract: Objective To compare bronchus and lung tissue damage of healthy mice after aerosol inhalation and intratracheal administration of amikacin and tigecycline. Methods One hundred and forty-four Kunming species of mice were randomly divided into 9 groups(16 mice per group): blank control group, normal saline inhalation group, amikacin low concentration inhalation group, amikacin high concentration inhalation group, tigecycline low concentration inhalation group, tigecycline high concentration inhalation group, normal saline intratracheal administration group, amikacin intratracheal administration group and tigecycline intratracheal administration group. Each group was given the corresponding treatment. Then bronchus and lung tissue pathological specimens of each group of mice were obtained. The bronchus and lung tissue damage was compared among each group. Results Alveolar damage scores of tigecycline high concentration inhalation group and amikacin high concentration inhalation group were significantly higher than that of blank control group(P=0.001; P<0.001). Alveolar damage scores of amikacin high concentration inhalation group was significantly higher than that of normal saline intratracheal administration group(P<0.001)and tigecycline intratracheal administration group(P=0.001). Conclusion Alveolar might be damaged by aerosol inhalation or intratracheal 山东大学学报 (医学版)55卷12期 -郑亮,等.雾化吸入及气管滴入阿米卡星、替加环素对健康小鼠支气管和肺组织的损伤 \=-administration of amikacin and tigecycline. The lung tissue damage after aerosol inhalation of amikacin might be more serious than intratracheal administration of tigecycline.

Key words: Aerosol inhalation, Intratracheal administration, Amikacin, Tigecycline, Bronchus, Lung tissue, Damage

中图分类号:

郑亮,亓倩,周玉法,李玉. 雾化吸入及气管滴入阿米卡星、替加环素对健康小鼠支气管和肺组织的损伤[J]. 山东大学学报 (医学版), 2017, 55(12): 24-30.

ZHENG Liang, QI Qian, ZHOU Yufa, LI Yu. Damage of bronchus and lung tissue in healthy mice after aerosol inhalation and intratracheal administration of amikacin and tigecycline[J]. Journal of Shandong University (Health Sciences), 2017, 55(12): 24-30.

参考文献 23

[1]	杨志刚, 马希涛, 雷小莉. 多药耐药非发酵菌的临床分布特点及耐药性分析[J]. 中华医院感染学杂志, 2014, 24(1): 25-27. YANG Zhigang, MA Xitao, LEI Xiaoli. Clinical distribution and drug resistance of multidrug-resistant non-fermenting bacteria[J]. Clin J Nosocomiol, 2014, 24(1): 25-27.
[2]	张亮, 周秋云, 陆磊, 等. 雾化吸入阿米卡星在气管支气管结核患者体内的药物分布特点[J]. 临床肺科杂志, 2017, 20(10): 44-47. ZHANG Liang, ZHOU Qiuyun, LU Lei, et al. Distribution characteristics of aerosolized inhaled amikacin in tracheobronchial tuberculosis patients[J]. Clinical Pulmonary Medicine, 2017, 20(10): 44-47.
[3]	Montgomery AB, Vallance S, Abuan T, et al. A randomized double-blind placebo-controlled dose-escalation phase 1 study of aerosolizedamikacin and fosfomycin delivered via the PARI investigational eFlow® inline nebulizer system in mechanically ventilated patients[J]. J Aerosol Med Pulm Drug Deliv, 2014, 27(6):441-448.
[4]	Lu Q, Yang J, Liu Z, et al. Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa[J]. Am J Respir Crit Care Med, 2011, 184(1): 106-115.
[5]	李虎, 杨春辉, 薛杨勇, 等. 雾化吸入抗生素治疗呼吸机相关性肺炎的临床疗效观察[J].中国呼吸与危重监护杂志, 2015, 14(3): 273-277. LI Hu, YANG Chunhui, XUE Yangyong, et al. Efficacy of nebulized antibiotics in treatment of ventilator-associated pneumonia[J]. Clin J Respir Crit Care Med, 2015, 14(3): 273-277.
[6]	Anthony KB, Fishman NO, Linkin DR, et al. Clinical and microbiological outcomes of serious infections with multidrug-resistant gram-negative organisms treated with tigecycline[J]. Clin Infect Dis, 2008, 46: 567-570. doi: 10.1086/526775.
[7]	李伟峰, 胡玉洁, 袁伟锋, 等. 气管内滴入与雾化博来霉素致小鼠肺纤维化模型的比较研究[J]. 南方医科大学学报, 2012, 32(2): 221-225. LI Weifeng, HU Yujie, YUAN Weifeng, et al. Comparison of two mouse models of lung fibrosis induced by intratracheal instillation and intratracheal aerosol administration of bleomycin[J]. J South Med Univ, 2012, 32(2): 221-225.
[8]	刘莹, 赖国祥, 周欣, 等. 阿米卡星经纤维支气管镜和静脉给药的药动学比较[J]. 中国医院药学杂志, 2003, 23(2): 97-98. LIU Ying, LAI Guoxiang, ZHOU Xin, et al. The pharmacokinetics of amikacin: comparison of intratracheal administration with intravenous infusion[J]. Chin Hosp Pharm J, 2003, 23(2): 97-98.
[9]	徐叔云. 药理实验方法学[M]. 3版. 北京:人民卫生出版社, 2003: 56.
[10]	Bosken CH, Wiqqs BR, Pare PD, et al. Small airway dimensions in smokers with obstruction to airflow[J]. Am Rev Respir Dis, 1990, 142(3):563-570.
[11]	Mikawa K, Nishina K, Takao Y, et al. ONO-1714, a nitric oxide synthase inhibitor, attenuates endotoxin-induced acute lung in rabbits[J]. Anesth Analg, 2003, 97(6): 1751-1755.
[12]	Sommerwerck U, Virella-Lowell I, Angyalosi G, et al. Long-term safety of tobramycin inhalation powder in patients with cystic fibrosis: phase IV(ETOILES)study[J]. Curr Med Res Opin, 2016, 32(11): 1789-1795.
[13]	Kaku N, Morinaga Y, Takada K, et al. Efficacy and pharmacokinetics of ME1100, a novel optimized formulation of arbekacin for inhalation, compared with amikacin in a murine model of ventilator-associated pneumonia caused by Pseudomonas aeruginosa[J]. J Antimicrob Chemother, 2016, pii: dkw517. doi: 10.1093/jac/dkw517.
[14]	Liu F, Li W, Pauluhn J, et al. Lipopolysaccharide-induced acute lung injury in rats: comparative assessment of intratracheal instillation and aerosol inhalation[J]. Toxicology, 2013, 304: 158-166. doi: 10.1016/j.tox.2012.12.020.
[15]	刘昌英, 晏彬, 谢国秀, 等. 雾化吸入氯化钠颗粒对呼吸道粘膜刺激实验的探讨[J]. 毒理学杂志, 2008, 22(6): 461-463. LIU Changying, YAN Bin, XIE Guoxiu, et al. Experimental study of nasal mucosal irritation induced by aerosolized sodium chloride granules[J]. Journal of Toxicology, 2008, 22(6): 461-463.
[16]	Reed MD, McCombie BE, Sivillo AE, et al. Safety assessment of nebulized xylitol in beagle dogs[J]. Inhal Toxicol, 2012, 24(6): 365-372.
[17]	Hrvacic B, Bosnjak B, Bosnar M, et al. Clarithromycin suppresses airway hyperresponsiveness and inflammation in mouse models of asthma[J]. Eur J Pharmacol, 2009, 616(1-3): 236-243.
[18]	文文, 赖国祥, 姚丽青, 等. 气管内给药对大鼠气管黏膜和肺组织影响的研究[J]. 中国内镜杂志, 2011, 17(10): 1028-1035. WEN Wen, LAI Guoxiang, YAO Liqing, et al. Investigation on injury of tunica mucosa tracheae and lung of rats induced by intratracheal drug administration[J]. Chin J Endosc, 2011, 17(10): 1028-1035.
[19]	Galvao AM, Wanderley MS, Silva RA, et al. Intratracheal co-administration of antioxidants and ceftriaxone reduces pulmonary injury and mortality rate in an experimental model of sepsis[J]. Respirology, 2014, 19(7): 1080-1087.
[20]	Takehara H, Makita M, Tanaka R, et al. Lung toxicity assessment using bronchoalveolar lavage fluid and pleural lavage fluid cytology by intratracheal treatment in rats[J]. J Toxicol Sci, 2014, 39(1): 141-145.
[21]	Kwon JT, Yang YS, Kang MS, et al. Pulmonary toxicity screening of triclosan in rats after intratracheal instillation[J]. J Toxicol Sci, 2013, 38(3): 471-475.
[22]	Haberl N, Hirn S, Wenk A, et al. Cytotoxic and proinflammatory effects of PVP-coated silver nanoparticles after intratracheal instillation in rats[J]. Beilstein J Nanotechnol, 2013, 4: 933-940. doi: 10.3762/bjnano.4.105.
[23]	苑少欣, 孔雅娴, 李蕊, 等. 气管滴注法与雾化吸入法建立小鼠急性肺损伤模型及其效果比较[J]. 中华实验和临床感染病杂志(电子版), 2014, 8(2): 8-12. YUAN Shaoxin, KONG Yaxian, LI Rui, et al. Establishment and effectiveness comparison of mouse models of acute lung injury by intratracheal instillation and aerosol inhalation[J]. Chin J Exp Clin Infect Dis(Electronic Edition), 2014, 8(2): 8-12.

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