首页|基于模型评价对慢性阻塞性肺疾病大鼠造模时间的优化

基于模型评价对慢性阻塞性肺疾病大鼠造模时间的优化

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目的 探索结合目前采用香烟烟熏(CS)联合气道滴注脂多糖(LPS)的方法构建慢性阻塞性肺疾病(COPD)大鼠模型的报道,探讨评价COPD大鼠模型的关键指标并优化造模时间.方法 采用CS联合气道滴注LPS的方法复制COPD大鼠模型,根据香烟烟熏时长将大鼠分为:空白4周组、空白8周组、空白12周组、模型4周组、模型8周组及模型12周组.观察记录大鼠一般情况及体重变化情况;采用小动物肺功能仪检测大鼠肺功能;采用酶联免疫吸附测定检测大鼠肺泡灌洗液中炎症因子肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的表达水平.结果 造模结束后,空白4周组、空白8周组和空白12周组大鼠体重分别明显高于模型4周组、模型8周组、模型12周组(P<0.05).模型4周组大鼠病理结果显示炎症细胞浸润;模型8周组大鼠病理结果显示炎症细胞浸润,部分肺泡隔断裂,肺泡融合;模型12周组大鼠病理结果显示炎症细胞浸润,大量肺泡隔断裂,肺泡融合.模型8周组大鼠FEV0.3/FVC%较空白8周组和显著降低(P<0.05);模型12周组FEV0.1/FVC%、FEV0.3/FVC%较空白12周组大鼠显著降低(P<0.05).空白4周组和模型4周组大鼠的0.1秒用力呼气容积(FEV0.1)/用力肺活量(FVC)、0.3秒用力呼气容积(FEV0.3)/FVC之间差异均无统计学意义(P>0.05).模型4周组、8周组、12周组TNF-α和IL-6较分别较空白4周组、8周组、12周组升高(P<0.05).结论 在评价COPD大鼠模型时,肺功能是关键性指标,单一的炎症指标并非造模成功的标志.CS暴露12周联合气道滴注LPS的方法可以建立更符合临床特征的COPD大鼠模型.
Optimization of COPD rat modeling time based on model evaluation
Objective To explore the key indicators for evaluating the rat model of chronic obstructive pulmonary disease(COPD)and optimize the modeling time in light of the current reports on the construction of COPD rat models by cigarette smoking(CS)combined with airway infusion of lipopolysaccharide(LPS).Methods The COPD rat model was replicated by CS combined with airway infusion of LPS.The rats were divided into 4-week blank group,8-week blank group,12-week blank group,4-week model group,8-week model group and 12-week model group according to the smoking duration.The general condition and body weight of the rats were observed and recorded.The lung function of rats was measured by small animal lung function apparatus.The expression lev-els of inflammatory factors tumor necrosis factor-α(TNF-α)and inter-leukin-6(IL-6)in alveolar lavage fluid of rats were detected by en-zyme-linked immunosorbent assay.Results After the modeling,the body weight of rats in 4,8 and 12 week blank group was signifi-cantly higher than that in 4,8 and 12 model week group,respectively(P<0.05).The pathological results of the 4-week model group showed inflammatory cell infiltration;The pathological results of the 8-week model group showed inflammatory cell infiltration,partial alveolar sep-tum rupture and alveolar fusion.The pathological results of the 12-week model group showed inflammatory cell infiltration,a large number of alveolar septa fractures,and alveolar fusion.Compared with 8-week blank group,FEV0.3/FVC%in 8-week model group was significantly decreased(P<0.05);FEV0.1/FVC%and FEV0.3/FVC%in 12-week model group were significantly lower than those in 12-week blank group(P<0.05).There were no significant differences in FEV0.1/FVC and FEV0.3/FVC between the 4-week blank group and 4-week model group(P>0.05).TNF-α and IL-6 in 4,8 and 12 week model group were higher than those in 4,8 and 12 week blank group,respectively(P<0.05).Conclusion Lung function is the key indicator in evaluating COPD rat model,and single inflammatory indicator is not the mark of successful model building.CS ex-posure for 12 weeks combined with airway infusion of LPS can establish a more clinically appropriate COPD rat model.

chronic obstructive pulmonary diseaserat modellung functionmodeling time

周子扬、陈颖、齐文川、陈道鸿、刘路、曾倩、赵凌

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610075 成都,成都中医药大学针灸推拿学院

慢性阻塞性肺疾病 大鼠模型 肺功能 造模时间

国家自然科学基金国家中医药局中医药创新团队及人才支持计划

82305008ZYYCXTD-D-202003

2024

医学研究生学报
南京军区南京总医院

医学研究生学报

CSTPCD北大核心
影响因子:1.652
ISSN:1008-8199
年,卷(期):2024.37(3)
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