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慢性阻塞性肺疾病大鼠模型的建立与评价 被引量:18

Establishment and evaluation of rat models of chronic obstructive pulmonary disease
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摘要 目的通过烟熏法、蛋白酶滴注及两者相结合的方法构建大鼠慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)模型,并从炎症水平、影像及病理等方面评价造模效果,对三种建模方法进行比较。方法使用烟熏、蛋白酶滴注及两者相结合的方法进行COPD大鼠造模,每组大鼠分别为60只、30只、30只,同时设置对照组20只。每周对大鼠进行体重测量。烟熏组及对照组大鼠于造模24 h,1、2、4、8、12、16、20、24周,蛋白酶组及蛋白酶+烟熏组大鼠于造模24 h,1、2、4、8、12周接受细胞因子检测、Micro-CT检查及病理检查。采用方差分析或Kruskal-Wallis H检验进行统计分析。结果第7周起烟熏组大鼠及蛋白酶+烟熏组大鼠体重增长较对照组明显减缓(P<0.05)。蛋白酶组及蛋白酶+烟熏组大鼠第24 h、1、2、4周的白细胞介素-10水平显著低于对照组(P<0.05)。蛋白酶组及蛋白酶+烟熏组大鼠第24 h的基质金属蛋白酶-9浓度显著大于对照组(P<0.05)。蛋白酶组、蛋白酶+烟熏组第4周及烟熏组第8周大鼠在Micro-CT图像及病理图像上均可观察到肺气肿改变。结论使用烟熏、蛋白酶及蛋白酶+烟熏的方法均可成功构建大鼠COPD模型。Micro-CT可灵敏真实的反应肺部病理改变。 Objective To establish rat models of chronic obstructive pulmonary disease(COPD)with smoking,protease instillation and smoking+protease instillation,and to evaluate and compare inflammation,imaging and pathology between these groups.Methods Rat models of COPD were established with smoking,protease instillation and smoking+protease instillation.There were 60 rats in the smoking group,30 rats in the protease group and 30 rats in the smoking+protease group.The control group contained 20 rats.Body weight was measured every week.In the smoking and control groups,five and two rats were euthanized,respectively at 24 h,and weeks 1,2,4,8,12,16,20 and 24 during the modeling process,and in the protease and smoking+protease groups,five rats were euthanized in each group at 24 h,and weeks 1,2,4,8 and 12.Rat lung tissues subjected to cytokine detection,micro-CT examination and pathological examination.Results The weight gain of rats in the smoking and smoking+protease group was significantly slower than the control group at week 7(P<0.05).The levels of IL-10 at 24 h,and weeks 1,2 and 4 were significantly lower in the protease group and the smoking+protease group compared with the control group(P<0.05).The concentration of MMP-9 at 24 h was significantly higher in the protease group and the smoking+protease group than the control group(P<0.05).Emphysema was observed on the micro-CT images and pathological images in the protease group and smoking+protease group at week 4,and in the smoking group at week 8.Conclusions Rat models of COPD can be successfully established by smoking,protease instillation and smoking+protease instillation.Micro-CT reflects changes in lungs with high sensitivity and validity.
作者 张迪 夏艺 范丽 刘士远 管宇 ZHANG Di;XIA Yi;FAN Li;LIU Shiyuan;GUAN Yu(Changzheng Hospital of the Second Military Medical University,Shanghai 200003,China)
出处 《中国实验动物学报》 CAS CSCD 北大核心 2020年第2期230-235,共6页 Acta Laboratorium Animalis Scientia Sinica
基金 国家自然科学基金(81871321,8137003,81501618,81501470)。
关键词 动物模型 肺疾病 慢性阻塞性 体层摄影术 X线计算机 animal model Pulmonary disease,chronic obstructive tomography,X-ray computed
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