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脂多糖诱导的小鼠急性呼吸窘迫综合征中microRNA-27a和PPARγ表达变化
Expression changes of microRNA-27a and PPARγ in LPS-induced acute respiratory distress syndrome mice
- 第三军医大学学报 2017年39卷第20期 页码：1967-1972
- 作者机构：
1.400038 重庆, 第三军医大学西南医院呼吸内科
2.400038 重庆, 第三军医大学基础医学部生物化学与分子生物学教研室
3.400042 重庆, 第三军医大学大坪医院野战外科研究所呼吸内科
- 作者简介：
[胡建林, E-mail: jianlinhu63@163.com HU Jianlin, E-mail: jianlinhu63@163.com
- 基金信息：国家自然科学基金面上项目(81670070)
DOI：10.16016/j.1000-5404.201706033
中图分类号： R-332;R363.21;R563.8收稿：2017-06-06，
修回：2017-07-11，
纸质出版：2017-10-30
- 稿件说明：
移动端阅览
朱端, 胡晨, 赵力, 等. 脂多糖诱导的小鼠急性呼吸窘迫综合征中microRNA-27a和PPARγ表达变化[J]. 第三军医大学学报, 2017,39(20):1967-1972.
Duan ZHU, Chen HU, Li ZHAO, et al. Expression changes of microRNA-27a and PPARγ in LPS-induced acute respiratory distress syndrome mice[J]. Journal of Third Military Medical University, 2017, 39(20): 1967-1972.
朱端, 胡晨, 赵力, 等. 脂多糖诱导的小鼠急性呼吸窘迫综合征中microRNA-27a和PPARγ表达变化[J]. 第三军医大学学报, 2017,39(20):1967-1972. DOI： 10.16016/j.1000-5404.201706033.
Duan ZHU, Chen HU, Li ZHAO, et al. Expression changes of microRNA-27a and PPARγ in LPS-induced acute respiratory distress syndrome mice[J]. Journal of Third Military Medical University, 2017, 39(20): 1967-1972. DOI： 10.16016/j.1000-5404.201706033.
摘要
目的
2
研究脂多糖(lipopolysaccharides
LPS)诱导小鼠急性呼吸窘迫综合征(acute respiratory distress syndrome
ARDS)模型中外周血和肺内microRNA-27a和过氧化物酶体增殖物激活受体γ(peroxisome proliferators-activated receptor-γ
PPARγ)表达变化规律，探讨microRNA-27a和PPARγ在ARDS发病机制中的作用。
方法
2
将50只8~10周雄性C57BL/6小鼠分为模型组不同给药时间(3、6、12、24 h各10只)和对照组(
n
=10)。通过尾静脉注射LPS建立ARDS模型，通过组织学病理评价、炎症反应细胞分泌物表达水平等炎症反应指标评价ARDS模型建立的有效性。Western blot和免疫组织化学(IHC)观察模型不同时间点肺内PPARγ表达及变化趋势；实时荧光定量PCR(qRT-PCR)进一步研究基因表达改变情况。
结果
2
与对照组相比，模型组不同时间点肺组织病理改变明显；外周血和肺内不同时间点microRNA-27a表达明显增加，外周血各时间点较变化对照组增加2~4倍，差异有统计学意义[3 h (3.53±0.89)
6 h (1.97±0.40)
12 h (1.87±0.35)
24 h (1.98±0.53)
P
<
0.05
]
。与对照组相比，肺内microRNA-27a 6 h(3.08±0.97)、24 h(3.49±0.94) 表达增加差异有统计学意义；3 h(1.90±0.87)、12 h(1.88±0.62) 差异无意义。PPARγ在蛋白水平表达明显减少；基因水平上外周血PPARγ 6、12 h表达降低差异有统计学意义[
P
<
0.05，6 h (0.31±0.19)
12 h (0.37±0.43)
]
，3(0.70±0.33)、24 h(0.80±0.44) 差异无统计学意义；肺内6、12、24 h表达降低差异有统计学意义[
P
<
0.05，6 h (0.60±0.23)
12 h (0.71±0.12)
24 h (0.42±0.20)
]
，3 h(0.67±0.36) 差异无统计学意义。
结论
2
LPS诱导小鼠ARDS模型中，microRNA-27a和PPARγ表达发生明显变化，二者可能参与ARDS发病过程。
Abstract
Objective
2
To determine the expression change patterns of microRNA-27a and peroxisome proliferator-activated receptor-γ (PPARγ) in peripheral blood and lung of acute respiratory distress syndrome (ARDS) mouse model induced by lipopolysaccharides (LPS)
and investigate their roles in the pathogenesis of ARDS.
Methods
2
Fifty (8~10 weeks old) healthy male C57BL/6 mice were assigned into the ARDS model group (
n
=40) and control group (
n
=10). The ARDS model was established by intravenously injection of
LPS in the tail (each time point
n
=10). Histopathological evaluation and expression changes of inflammatory proteins were used for assessing the effectiveness of model establishment. Western blotting and immunohistochemistry (IHC) were performed to determine the expression profile of PPARγ over time in the lungs of the ARDS mice. The mRNA levels of microRNA-27a and PPARγ were detected by real-time quantitative polymerase chain reaction (qRT-PCR).
Results
2
The IHC assay showed obvious pathological changes of lung tissues at different time points in the ARDS model group compared with the control. The expression of microRNA-27a was remarkably increased over time in the peripheral blood and lung. In the peripheral blood
the increase was 2-4 fold higher than the control
which was statistically significant at all time points (3 h: 3.53±0.89
6 h: 1.97±0.40
12 h: 1.87±0.35
24 h: 1.98±0.53
(
P
<
0.05). In the lung tissue
the increased expression of microRNA-27a was significant at 6 h (3.08±0.97) and 24 h (3.49±0.94
both
P
<
0.05)
but not at 3 h(1.90±0.87) and 12 h(1.88±0.62). PPARγ expression was reduced in both mRNA and protein levels. In the peripheral blood
the decrease of mRNA PPARγ between the two groups was significant at 6 h(0.31±0.19) and 12 h (0.37±0.43
both
P
<
0.05)
but not at 3 h (0.70±0.33) and 24 h(0.80±0.44). In the lung tissue
the reduced mRNA PPARγ level at 6 h(0.60±0.23)
12 h(0.71±0.12) and 24 h (0.42±0.20) hours was statistically significant (
P
<
0.05)
but not at 3 h (0.67±0.36).
Conclusion
2
In the LPS-induced ARDS mice
expression of microRNA-27a and PPARγ is significantly changed
indicating their participation in the pathogenesis of ARDS.
关键词
Keywords
references
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