Icariin reduces LPS-induced acute lung injury in mice undergoing bilateral adrenalectomy by regulating GRα
| Autor: | Jingcheng Dong, Yijie Du, Xianjun Sun, Baojun Liu, HuiQin Cheng, Jianhua Huang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Male medicine.medical_specialty Lipopolysaccharide medicine.medical_treatment Acute Lung Injury Lung injury Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Glucocorticoid receptor Receptors Glucocorticoid Downregulation and upregulation Corticosterone Internal medicine Medicine Animals STAT3 Lung Pharmacology Flavonoids Mice Inbred BALB C biology business.industry Adrenalectomy respiratory system respiratory tract diseases Disease Models Animal 030104 developmental biology Endocrinology chemistry biology.protein business 030217 neurology & neurosurgery Drugs Chinese Herbal |
| Zdroj: | European journal of pharmacology. 876 |
| ISSN: | 1879-0712 |
| Popis: | In the present study, we established the acute lung injury (ALI) model of mice with adrenal insufficiency, and to investigate the possible mechanism by which Icariin (ICA) reduces lipopolysaccharide (LPS) -induced ALI in mice undergoing bilateral adrenalectomy by regulating glucocorticoid receptor α (GRα). ALI of BALB/c mice with adrenal insufficiency was induced by LPS and bilateral adrenalectomy (ADX). The pathological and morphological changes in lung tissues were observed, the levels of corticosterone, IL-6, and TNF-α in serum and lung tissues by ELISA. The levels of GRα, IL-6, TNF-α, NF-κB p65, Stat3, and c-Jun in lung tissues were detected by RT-qPCR and Western Blotting, GRα activity was blocked by GRα antagonist RU486. It was found that the dual intervention of LPS and ADX had further aggravation the downregulation of GRα and upregulation of NF-κB p65, c-Jun, Stat3, and IL-6 and TNF-α, ICA enhanced the expression of GRα in lung tissues and inhibited the expression of NF-κB p65, c-Jun, Stat3, IL-6, and TNF-ɑ, thereby reducing ALI. However, RU486 could partially counteract the protective effect of ICA on lung injury and its downregulating effect on various inflammatory transcription factors and inflammatory cytokines. In conclusion, ICA reduces ALI in mice undergoing bilateral ADX by regulating GRα, and no inhibitory effect on hypothalamic pituitary adrenal (HPA) axis. |
| Databáze: | OpenAIRE |
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