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收稿:2019-12-06,
纸质出版:2020-04-30
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薛坤娇, 阮玲瑛, 胡婕, 等. 糖皮质激素调控Keap1-Nrf2通路减轻哮喘小鼠肺氧化应激反应的作用研究[J]. 第三军医大学学报, 2020,42(8):807-814.
Kunjiao XUE, Lingying RUAN, Jie HU, et al. Glucocorticoid regulates Keap1-Nrf2 pathway to relieve pulmonary oxidative stress in asthmatic mice[J]. Journal of Third Military Medical University, 2020, 42(8): 807-814.
薛坤娇, 阮玲瑛, 胡婕, 等. 糖皮质激素调控Keap1-Nrf2通路减轻哮喘小鼠肺氧化应激反应的作用研究[J]. 第三军医大学学报, 2020,42(8):807-814. DOI: 10.16016/j.1000-5404.201912057.
Kunjiao XUE, Lingying RUAN, Jie HU, et al. Glucocorticoid regulates Keap1-Nrf2 pathway to relieve pulmonary oxidative stress in asthmatic mice[J]. Journal of Third Military Medical University, 2020, 42(8): 807-814. DOI: 10.16016/j.1000-5404.201912057.
Objective
2
To investigate the level of oxidative stress in asthmatic mice and the mechanism of dexamethasone forrelieving oxidative stress.
Methods
2
Thirty female C57BL/6 mice were randomly divided into control group
asthma group and dexamethasone group. Following challenges with house dust mites in the latter 2 groups and prior dexamethasone treatment in dexamethasone group
the mice were examined for expression levels of lipid peroxide metabolites malondialdehyde (MDA) and oxidized glutathione (GSSG). Quantitative real-time PCR was used to detect the expression of nuclear factor erythroid 2-related factor 2 (NF-E2) and heme oxygenase 1 (HO-1) in the lung tissues. Immunohistochemistry was used to detect the expression of Nrf2 protein
and Western blotting was performed to detect the changes of Nrf2-Keap1 signaling pathway in the lungs of the mice.
Results
2
MDA and GSSG levels were significantly higher in the asthmatic mice than in control group (
P
<
0.01)
and were significantly lowered by dexamethasone treatment in the asthmatic mice (
P
<
0.05). Compared with the control group
the asthmatic mice showed significantly higher pulmonary expression levels of Nrf2 and HO-1 mRNA (
P
<
0.05)
which were obviously lowered by dexamethasone treatment (
P
<
0.05). Immunohistochemistry and immunofluorescence assay revealed a significantly highe
r expression of Nrf2 protein in the lung tissue of asthmatic mice (
P
<
0.01)
which was significantly lowered by dexamethasone treatment (
P
<
0.01). The asthmatic mice had a significantly lower expression of Keap1 protein in the lungs (
P
<
0.05)
which was obviously increased by dexamethasone treatment (
P
<
0.05).
Conclusion
2
Asthmatic mice have an increased level of oxidative stress. Dexamethasone inhibits the level of pulmonary oxidative stress in asthmatic mice possibly by inhibiting the expression of the downstream antioxidant elements
via
regulating the Keap1-Nrf2 pathway.
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