新型MWCNTs滴鼻法有效构建了肺炎及纤维化小鼠模型  

A Novel Repeated Nasal Drops Method Constructs Efficiently MWCNTs-induced Pulmonary Inflammation and Fibrosis Mouse Model

作　　者：章静 张佳震 ZHANG Jing;ZHANG Jiazhen(School of Medicine,Anhui University of Science and Technology,Huainan Anhui 232001,China)

机构地区：[1]安徽理工大学医学院,安徽淮南232001

出　　处：《安徽理工大学学报(自然科学版)》2025年第1期99-108,共10页Journal of Anhui University of Science and Technology:Natural Science

基　　金：安徽省自然科学基金资助项目(2008085MH261,2208085QH282)。

摘　　要：目的拟通过滴鼻法建立一种新型可重复MWCNTs暴露小鼠模型,它既方便、快速、经济,而且可重复使用。以期对未来肺纤维化药物的研究和机制探索提供更加高效的模型支持。方法将80μL(125μg/mL)的MWCNTs悬液暴露于C57BL/6小鼠中,连续14d,并评估其生理状态。采用ELISA、HE染色、Masson染色和免疫荧光双染色等方法分析小鼠第3、7、14、28d的肺病变。最后,采用一种新的肺损伤碳纳米管暴露评分系统对实验数据进行分析和聚类分析。结果病理切片中观察到暴露后在第7d形成肺部炎症,在暴露后第14d形成纤维化。只有到第28d,肺纤维化达到最严重,小鼠处于最糟糕的生理状态。与口咽灌注法相比鼻滴注模型大大缩短了广泛纤维化的形成时间。MWCNTs暴露通过激活TGF-β1/Smad2/3信号通路,增加了FMT相关标志物(α-SMA和Col-I)和促炎因子TGF-β1的特异性过程。聚类分析将该模型的病理生理过程定义为:初始阶段、炎症期、进展期和纤维化期。结论本研究通过建立一个新的MWCNTs暴露小鼠模型,探讨了重复滴鼻液方法在碳纳米管暴露患者肺部诱导炎症和产生纤维化中的关键重要性。Objective The aim is to develop a new reproducible MWCNTs exposure mouse model,which is convenient,fast,economical and reusable.In order to provide more efficient model support for the future research and mechanistic exploration of pulmonary fibrosis drugs.Methods 80μL of(125μg/mL)MWCNTs suspension was exposed in C57BL/6 mice for 14 days and assessed their physiological status.Lung lesions in mice on days 3,7,14,and 28 were analyzed by ELISA,HE staining,Masson staining and immunofluorescence double staining.Finally,the experimental data were analyzed and clustered by using a new exposure scoring system for lung injury CNTs.Results The pulmonary inflammation formed on day 7,and the fibrosis formed on day 14 after exposure.Only on day 28 did pulmonary fibrosis reach its worst severity and the mice were in their worst physiological state.Compared with the oropharyngeal perfusion method,the nasal infusion model greatly reduced the formation time of extensive fibrosis.MWCNTs Exposure increased the specific process of FMT-related markers(α-SMA and Col-I)and the proinflammatory factor TGF-β1 through the activation of the TGF-β1/Smad2/3 signaling pathway.Cluster analysis defined the pathophysiological process of this model as:initial stage,inflammatory phase,progressive stage and fibrotic stage.Conclusion This study addressed the critical importance of repeated nasal drops in lung induction of inflammation and generation of fibrosis in CNT-exposed patients by establishing a novel mouse model of MWCNTs exposure.

关 键 词：鼻滴 肺纤维化 碳纳米管 模型建立 

分 类 号：R392-3[医药卫生—免疫学]