摘要
目的建立免疫抑制小鼠侵袭性肺曲霉病动物模型用于相关基础与临床研究。方法ICR小鼠腹腔注射不同剂量环磷酰胺和皮下注射一定剂量地塞米松磷酸钠，建立免疫抑制状态；予小鼠两鼻孔接种烟曲霉AF293，观察96h存活率和不同时间点肺组织的病理变化。结果两次环磷酰胺（150＋150）mg／kg和一次地塞米松磷酸钠50mg／kg剂量注射组，中性粒细胞数降低达到预期水平，连续4d低于100／μl；烟曲霉分生孢子悬液10倍稀释后浓度约1×10^8／ml接种小鼠，96h后小鼠存活率为83．3％；肺组织病理观察在72h时曲霉孢子聚积并生成菌丝，肺组织有肉芽肿形成；96h时孢子大量繁殖，肺组织出血坏死，偶见肺脓肿形成。结论通过免疫抑制剂成功建立了免疫抑制小鼠，并且通过鼻腔感染曲霉菌获得稳定的肺曲霉病小鼠模型。
Objective To establish animal model of invasive pulmonary aspergillosis in immunosuppressed mice which would be used in preclinical and clinal research. Methods In order to get immunosuppressed mice, ICR mice were administrted different doses of cyclophosphamide （CPA） intraperitoneally, and dexamethasone sodium phosphate subcutaneously, the consecutive change of leukocytes and neutrophils in mice peripheral blood were observed. Aspergillus fumigatus AF293 was inoculated by nostril drop of each mouse to generate invasive pulmonary aspergillosis. The death and behaviors of mice after infection were recorded. All mice were killed at different time points and the lung tissue was analyzed histopathologically. Results The neutrophils counts in （150 ＋ 150）mg/kg CPA doses group decreased to less than 100/μl and lasted for 4 days. The survival rate of mice was 83.3% in 96 hours after inoculation concentration of fungal conidiospore suspension with concentration about 1 × 10^8/ml. A great deal of A.fumigatus were observed and fungal granuloma appeared at 72h in mice lung tissue. A.fumigatus multipli highest density at 96h, tissue necrosis and pulmonary abscess appeared at 96h. Conclusion Immunosuppres ed to the sed mice were induced by CPA and dexamethasone administration in combination, and invasive pulmonary aspergillosis were established successfully by dropping A. fumigatus AF293 into the nares of each mouse.
出处
《中国抗生素杂志》
CAS
CSCD
北大核心
2009年第4期I0003-I0007,共5页
Chinese Journal of Antibiotics
关键词
烟曲霉
侵袭性肺曲霉病
动物模型
ICR小鼠
Aspergillusfumigatus
Invasive pulmonary aspergillosis
Animal model
ICR mice
作者简介
于利玲，女，生于1983年，在读硕士研究生。
通讯作者，E-mail：xiao—yonghong@163．com
