Astragaloside IV Attenuates Lipopolysaccharides-Induced Pulmonary Epithelial Cell Injury through Inhibiting Autophagy
| Autor: | Liu Biwang, Yanmiao Ma, Zhang Huizhong, Yonghui Wang, Zhao Huan |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Lipopolysaccharides
Necrosis Cell Survival ATG5 Anti-Inflammatory Agents Respiratory Mucosa Pharmacology medicine.disease_cause 030226 pharmacology & pharmacy Cell Line Flow cytometry Mice 03 medical and health sciences 0302 clinical medicine Autophagy medicine Animals Viability assay Respiratory Distress Syndrome medicine.diagnostic_test Chemistry Epithelial Cells Lung Injury General Medicine Saponins Triterpenes Oxidative Stress Apoptosis Tumor necrosis factor alpha medicine.symptom 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Pharmacology. 105:90-101 |
| ISSN: | 1423-0313 0031-7012 |
| Popis: | Background: Astragaloside IV has shown its promising effect on acute respiratory distress syndrome (ARDS). Objectives: We aim to explore whether astragaloside IV is effective for ARDS treatment in a lipopolysaccharides (LPS)-induced cell model and whether autophagy is involved in the therapeutic function of astragaloside IV. Methods: MLE-12 cells were induced by LPS to construct an ARDS model in vitro. Cell viability was estimated by cell counting kit-8 and cell apoptosis by flow cytometry. Lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured by enzyme-linked immunosorbent assay kit. The expression of tumour necrosis factor (TNF)-α, interleukin (IL)-6, zonula occludens (ZO)-1, Beclin-1 and autophagy-related (atg) 5 mRNA was evaluated by quantitative PCR, and the expression of ZO-1, microtubule-associated proteins 1A/1B light chain 3B (LC3B) I and, LC3B II protein by Western blot. Results: LPS effectively inhibited cell viability and LC3B I expression and enhanced LC3B II, Beclin-1 and atg5 expressions in MLE-12 cells. In LPS-induced ARDS cell model, astragaloside IV up-regulated cell viability, SOD activity and ZO-1 and LC3B I expressions but down-regulated cell apoptosis, TNF-α, IL-6, LC3B II, Beclin-1 and atg5 expressions and LDH and MDA levels. 3-methyladenine promoted cell viability and ZO-1 expression, down-regulated Beclin-1 and atg5 expression, while Rapamycin (Rap) had an opposite effect. Astragaloside IV suppressed cell viability and ZO-1 expression after the Rap treatment. Conclusions: Astragaloside IV might suppress autophagy initiation directly or indirectly through suppressing the oxidative stress and inflammatory response, which further enhances the cell viability and tight junction and reduces apoptosis in LPS-stimulated pulmonary endothelial ARDS cell model, thus exerting its therapeutic function in ARDS. |
| Databáze: | OpenAIRE |
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