不同免疫抑制剂对小鼠罹患侵袭性肺曲霉病的影响

摘要/Abstract

摘要：

目的比较两种免疫抑制状态造成侵袭性曲霉感染（IPA）后天然免疫反应的异同。方法清洁级雄性BALB/c小鼠，分别使用地塞米松（A组）及环磷酰胺（B组）预处理后气道接种烟曲霉孢子建立IPA模型。观察小鼠存活率，肺病理检查，评估肺部及肺外脏器真菌负荷；支气管肺泡灌洗液（BALF）检测促炎、抗炎细胞因子浓度。结果 A组小鼠平均生存期与B组比较有显著差异。病理提示A组小鼠肺组织有大量炎症细胞聚集；B组可见到典型的曲霉菌丝浸润性生长。B组小鼠肺部烟曲霉CFU、烟曲霉18s rRNA较A组升高；B组肺外各脏器与A组比较均具有统计学差异。检测BALF中炎症因子：A组TNF-α未检测到，IL-10峰值在72 h出现，IL-1α自第一天起即升高，第3天达峰值；B组TNF-α及IL-10在24 h后均明显升高，于48 h达峰值；IL-1α一直在低水平维持；B组与各组间比较，TNF-α、IL-1α及IL-10均有显著差异。A、B两组IL-1β表达在接种烟曲霉后均迅速升高，并一直在高水平维持，两组间无差异。结论不同预处理造成小鼠免疫抑制后建立IPA模型，激素组肺部出现明显的炎症反应；环磷酰胺组可出现显著的全身真菌播散。

关键词: 侵袭性曲霉感染, 动物模型, 小鼠, 免疫, 致病机制

Abstract:

Objective To establish an experimental immunosuppressed mice model of invasive pulmonary aspergillosis (IPA),to evaluated various parameters of the innate immune response during the progression of IPA.Methods Immunosuppressed mice received the intratracheal administration of A.fumigatus conidia after two immunosuppressive treatments:a corticosteroid (group A) and a cyclophosphamidum agent (group B).We compared host responses 24 h,48 h and 72 h after infection in terms of survival,lung tissue histopathological analysis,fungal burden,pulmonary production of pro-and anti-inflammatory cytokines.Results The group A showed longer survival than group B did (5.33 vs 2.5 d,P<0.05).Group A showed severe bleeding and congestive,and lung tissue granuloma formation;while group B showed visible A.fumigatus hyphae,tissue necrosis 48 h after infection.Through CFUs and A.fumigatus 18sRNA detections,fugal burdens were significantly lower in lungs of corticosteroid-treated mice than those of cyclophosphamidum-treated mice.This difference was also observed in livers and kidneys,indicating that the level of fungal dissemination was higher in group B than that of group A.In group B mice,the IL-10 concentration increased by 48 h after infection and peaked at 72 h (86+15 pg/mL).No TNF-α production was detected.In group A mice,both TNF-α and IL-10 were detected at very high concentrations at 48 h (3 120±393,434±97 pg/mL).IL-1α expression increased 24 h after infection in group A mice and continually increased within the 3 days.But in group B,IL-1α concentrations maintained with low level.In both group A and B,the expressions of IL-1β increased dramatically after infection.Conclusion Establishing the IPA animal models of the mice by corticosteroid and chemotherapy-treated,We found that IPA pathogenesis was difference between the two groups:the inflammation response of lung was severe in corticosteroid-treated mice than those in chemotherapy-treated mice,while chemotherapy-treated mice showing an adverse host response.

Key words: invasive pulmonary aspergillosis, animal model, mice, immunology, pathology

中图分类号:

R519.8

陈玉宝, 陈菲菲, 邹春芳, 邵宏涛. 不同免疫抑制剂对小鼠罹患侵袭性肺曲霉病的影响[J]. 中国真菌学杂志, 2017, 12(3): 135-139.

CHEN Yu-bao, CHEN Fei-fei, ZOU Chun-fang, SHAO Hong-tao. Comparison of two immunosuppressive agents on the infection and inflammation of experimental invasive pulmonary aspergillosis mice models[J]. Chinese Journal of Mycology, 2017, 12(3): 135-139.

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