Inhibiting the ROCK Pathway Ameliorates Acute Lung Injury in Mice following Myocardial Ischemia/reperfusion
| Autor: | Weixin Meng, Shangdian Liu, Yagudin Timur, Dong-Yun Qiu, Bo Sun, Lei Xu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Immunology Acute Lung Injury Apoptosis Myocardial Reperfusion Injury Lung injury medicine.disease_cause Andrology Superoxide dismutase 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine medicine Animals chemistry.chemical_classification Glutathione Peroxidase TUNEL assay medicine.diagnostic_test biology Chemistry Superoxide Dismutase Glutathione peroxidase General Medicine Malondialdehyde Disease Models Animal 030104 developmental biology Bronchoalveolar lavage Terminal deoxynucleotidyl transferase 030220 oncology & carcinogenesis biology.protein Oxidative stress |
| Zdroj: | Immunological investigations. 51(4) |
| ISSN: | 1532-4311 |
| Popis: | To clarify the role of Y-27632, a selective inhibitor of Rho-associated coiled-coil forming protein kinase (ROCK), in acute lung injury (ALI) induced by myocardial ischemia/reperfusion (I/R). Mice were randomized into Sham, I/R, and Y-27632 (10, 20 or 30 mg/kg) + I/R groups, and hemodynamics, infarcted area, the protein concentration, neutrophils in bronchoalveolar lavage fluid (BALF), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels were assessed. Pathological changes were evaluated by hematoxylin-eosin (HE) staining; protein and gene expression were measured by Western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry and quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR); and apoptosis was assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining. ROCK1 and ROCK2 expression was up-regulated in lung tissues of I/R mice compared to sham mice. Y-27632 decreased the protein concentration and the neutrophils in BALF in I/R mice, improved hemodynamics and reduced infarct size (IS)/area at risk (AAR) ratio. In addition, pathological changes in lung tissues of Y-27632-treated mice were mitigated, and these alterations were accompanied by decreases in MDA levels in lung tissues and increases in SOD and GSH-Px levels. Moreover, in I/R group, the number of apoptotic cells in lung tissue was higher than that in sham group, and p53, Caspase-3 and Bax expression was up-regulated; however, following treatment with Y-27632 (10, 20 and 30 mg/kg), these changes were reversed. Inhibition of ROCK pathway by Y-27632 ameliorated ALI in myocardial I/R mice by mitigating oxidative stress, inflammation and cell apoptosis. |
| Databáze: | OpenAIRE |
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