1.400038 重庆, 陆军军医大学(第三军医大学)第一附属医院: 老年医学与特勤医学科
2.400038 重庆, 陆军军医大学(第三军医大学)第一附属医院: 感染科
3.400038 重庆, 陆军军医大学(第三军医大学)第一附属医院: 呼吸内科
Received:16 January 2023,
Revised:2023-02-09,
Published:15 May 2023
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Wu LI, Yunhua LIU, Tuo SHI, et al. Establish of a mouse model of COPD that meets clinical criteria by LPS+cigarette smoke exposure for 12 weeks[J]. Journal of Army Medical University, 2023, 45(9): 982-988.
Wu LI, Yunhua LIU, Tuo SHI, et al. Establish of a mouse model of COPD that meets clinical criteria by LPS+cigarette smoke exposure for 12 weeks[J]. Journal of Army Medical University, 2023, 45(9): 982-988. DOI: 10.16016/j.2097-0927.202301084.
目的
2
探究用脂多糖(lipopolysaccharide
LPS)联合香烟烟雾(cigarette smoke
CS)诱导12周可否成功构建符合临床标准的慢性阻塞性肺疾病(chronic obstructive pulmonary disease
COPD)小鼠模型。
方法
2
选取8周龄雄性C57BL/6小鼠30只
体质量20~25 g
分为模型组和对照组。采用LPS+CS联合诱导进行造模
在第1、14天使用LPS (2 mg
/kg)气管内给药
给药当天不给予CS
其余时间小鼠暴露于CS中吸烟2次/d (10支、60 min/次)。LPS+CS联合诱导12周的小鼠为模型组(
n
=15)
未进行干预的同批次小鼠为对照组(
n
=15)。造模后对比两组小鼠肺组织病理(HE、Masson染色)、炎症因子(IFN-γ、IL-12、TNF-α、IL-6)和肺功能(FEV
0.1
/FVC%)的变化。
结果
2
与对照组相比
LPS+CS诱导后小鼠肺组织病理显示支气管平滑肌层纤维化、肺泡膈断裂、肺泡融合
平均肺泡截距显著增大(
P
<
0.05)
平均肺泡数显著减少(
P
<
0.05)
全身和肺部促炎炎症因子IFN-γ、IL-12、TNF-α、IL-6均明显增多
肺功能FEV
0.1
/FVC%明显降低(
P
<
0.05)
平均肺泡截距和FEV
0.1
/FVC%极其显著负相关(
r
=-0.922 6
P
<
0.001)
而平均肺泡数和FEV
0.1
/FVC%呈极其显著正相关(
r
=0.933 0
P
<
0.001)。
结论
2
采用LPS+CS诱导12周可以成功建立符合临床标准的COPD小鼠模型。
Objective
2
To investigate whether the induction of lipopolysaccharide (LPS) combined with cigarette smoke (CS) for 12 weeks can successfully construct a mouse model of chronic obstructive pulmonary disease (COPD) that meets clinical criteria.
Methods
2
Thirty male C57BL/6 mice (8 weeks old
20~25 g) were subjected and randomly divided into model (
n
=15) and control groups (
n
=15).A combined induction of LPS+CS was used for modeling
and LPS (2 mg/kg) was administered intratracheally only on days 1 and 14
while CS exposure (2 times/d
10 cigarettes
60 min/time) was conducted on the other days during the induction for 12 weeks.The same batch of mice were given no intervention and served as the control group.Changes in lung histopathology (HE and Masson staining)
inflammatory factor levels (IFN-γ
IL-12
TNF-α and IL-6) and lung function (FEV
0.1
/FVC%) were compared between the 2 groups of mice after modeling.
Results
2
When compared with the control group
LPS+CS induction resulted in obvious fibrosis of bronchial smooth muscle layer
alveolar diaphragm dissection
alveolar fusion
and significantly increased mean alveolar intercept (
P
<
0.001)
obviously decreased mean alveolar number (
P
<
0.001)
notably elevated systemic and pulmonary pro-inflammatory factors IFN-γ
IL-12
TNF-α and IL-6 levels
and reduced FEV
0.1
/FVC% value (
P
<
0.001).Mean alveolar intercept and FEV
0.1
/FVC% were extremely significantly negatively correlated (
r
=-0.922 6
P
<
0.001)
while mean alveolar number and FEV
0.1
/FVC% had extremely significant positive correlation (
r
=0.933 0
P
<
0.001).
Conclusion
2
A mouse model of COPD that meets clinical criteria can be established successfully with LPS+CS induction for 12 weeks.
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