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烟草烟雾与机动车尾气暴露建立的大鼠慢性阻塞性肺疾病模型比较

A comparative study of chronic obstructive pulmonary disease models in rats established by exposure to cigarette smoke and motor vehicle exhaust
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摘要 目的对比烟草烟雾(CS)暴露和机动车尾气(MVE)暴露两种方法构建的大鼠慢性阻塞性肺疾病(COPD)模型的模拟程度。方法将24只雄性SD大鼠按随机数字表分为对照组、CS组与MVE组,每组8只。CS组与MVE组大鼠分别采用CS或MVE暴露建立COPD模型。建模结束后,检测各组大鼠的肺功能;收集大鼠支气管肺泡灌洗液(BALF),检测其中炎性细胞数、炎性因子白细胞介素(IL)-6和肿瘤坏死因子(TNF)-α及黏蛋白5AC(MUC5AC)含量;HE染色观察肺组织和气道病理变化;PAS染色检测气道杯状细胞增生情况。结果与对照组比较,CS组和MVE组大鼠的肺功能参数吸气阻力(RI)、肺总量(TLC)、肺静态顺应性(Cchord)均明显增高(P<0.05),而呼气流速参数FEV50/FVC明显降低(P<0.05);与MVE组相比,CS组大鼠的RI、TLC、Cchord均明显增高(P<0.05),FEV50/FVC降低(P<0.05)。肺组织HE染色结果显示,CS组和MVE组大鼠平均肺泡截距(MLI)均高于对照组(P<0.05),CS组MLI高于MVE组(P<0.05)。CS组和MVE组大鼠BALF中白细胞、中性粒细胞、巨噬细胞和淋巴细胞数,以及IL-6、TNF-α含量均高于对照组(P<0.05);且CS组中炎性细胞数、IL-6及TNF-α含量均高于MVE组(P<0.05)。肺组织PAS染色结果显示,CS组和MVE组大鼠大气道杯状细胞较对照组均明显增多(P<0.05),且CS组杯状细胞数高于MVE组(P<0.05);CS组和MVE组BALF中MUC5AC含量均高于对照组(P<0.05),且CS组大鼠BALF中MUC5AC含量高于MVE组(P<0.05)。结论应用CS或MVE暴露均可建立大鼠COPD模型,但CS暴露比MVE暴露能更好地模拟COPD急性加重期特征。 Objective To compare the fidelity of chronic obstructive pulmonary disease(COPD) models established using two methods:exposure to cigarette smoke(CS) and exposure to motor vehicle exhaust(MVE) in rats.Methods Twenty-four male SD rats were randomly divided into control,CS-exposed(CS),and MVE-exposed(MVE) groups,with 8 rats per group.Rats in CS and MVE groups were exposed to CS or MVE,respectively,to induce COPD models.After COPD model established,lung function of each group was assessed.Bronchoalveolar lavage fluid(BALF) was collected to measure inflammatory cell counts,levels of inflammatory cytokines interleukin-6(IL-6) and tumor necrosis factor(TNF)-α,and expression levels of mucin 5AC(MUC5AC).Lung tissue sections were stained with hematoxylin and eosin(HE) to observe pulmonary tissue and airway pathological changes.Periodic acid-Schiff(PAS) staining was used to detect goblet cell hyperplasia in airways.Results Compared with control group,rats in CS and MVE groups showed significantly increased inspiratory resistance(RI),total lung capacity(TLC),and lung static compliance(Cchord)(P<0.05),while expiratory flow parameters FEV50/FVC were significantly decreased(P<0.05).Compared with MVE group,rats in CS group had significantly higher RI,TLC,and Cchord(P<0.05),and lower FEV50/FVC(P<0.05).HE staining of lung tissues showed that mean linear intercept(MLI) was significantly higher in both CS and MVE groups compared with control group(P<0.05),with CS group having higher MLI than MVE group(P<0.05).BALF analysis revealed that white blood cells,neutrophils,macrophages,lymphocytes,IL-6,and TNF-α levels were significantly higher in both CS and MVE groups compared with control group(P<0.05),and inflammatory cell counts,IL-6,and TNF-α levels were higher in CS group compared with MVE group(P<0.05).PAS staining of lung tissues indicated that goblet cells in large airways were significantly increased in both CS and MVE groups compared with control group(P<0.05),with CS group showing higher goblet cell counts than MVE group(P<0.05).Expression levels of MUC5AC in BALF were significantly higher in both CS and MVE groups compared with control group(P<0.05),with CS group having significantly higher MUC5AC levels than MVE group(P<0.05).Conclusions Exposure to CS or MVE can establish a rat model of COPD,with CS exposure better mimicking characteristics of acute exacerbation of COPD compared to MVE exposure.
作者 李德富 叶园园 章洪萍 侯润华 何耀军 张春云 胡杰英 陈蕊 Li De-Fu;Ye Yuan-Yuan;Zhang Hong-Ping;Hou Run-Hua;He Yao-Jun;Zhang Chun-Yun;Hu Jie-Ying;Chen Rui(Department of Critical Care Medicine,the Fifth Affiliated Hospital of Guangzhou Medical University/Guangdong Key Laboratory of Biological Targeted Diagnosis,Treatment and Rehabilitation,Guangzhou,Guangdong 510700,China;Department of Respiratory Medicine,the First Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong 510120,China;Department of Critical Care Medicine,General Hospital of Southern Theater Command,Guangzhou,Guangdong 510010,China)
出处 《解放军医学杂志》 CAS CSCD 北大核心 2024年第9期1038-1044,共7页 Medical Journal of Chinese People's Liberation Army
基金 国家自然科学基金(81900033) 广东省自然科学基金(2022A1515012504) 广州市基础研究计划项目(202201020513) 广州市医学重点学科(2021-2023项目)。
关键词 慢性阻塞性肺疾病 烟草烟雾 机动车尾气 动物模型 chronic obstructive pulmonary disease cigarette smoke motor vehicle exhaust animal model
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