RESUMEN
Vitamin D supplementation is reported to have anti-inflammatory and neuroprotective effects during cerebral ischemia-reperfusion injury (CIRI), but the protective mechanism has not been fully elucidated. In this study, rats were given prior administrations of 1,25-vitamin D3 (1,25-VitD3) for a week and subjected to 2 hours of middle cerebral artery occlusion (MCAO) followed by 24 hours of reperfusion. Supplementation with 1,25-VitD3 significantly reduced neurological deficit scores and cerebral infarction areas, and increased surviving neurons. Oxygen-glucose deprivation/reoxygenation (OGD/R)-induced rat cortical neuron cells (RN-C) were subjected to 1,25-VitD3 treatment. Administration of 1,25-VitD3 improved cell viability and inhibited lactate dehydrogenase (LDH) activity and cell apoptosis in OGD/R-stimulated RN-C, as assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-h-tetrazolium bromide (MTT) assay, LDH activity assays and TdT-mediated dUTP nick end labeling (TUNEL) staining, respectively. Notably, western blot assay showed that 1,25-VitD3 upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) to alleviate oxidative stress, but reduced proteins and inflammatory cytokines related to NLR pyrin domain containing 3 (NLRP3)-mediated pyroptosis, resulting in decreased pyroptosis and neuroinflammation in vivo and in vitro. Transfection of pcDNA-Nrf2 in RN-C also inhibited pyroptosis and OGD/R-induced cell death whereas breakdown of Nrf2 signals destroyed the protective effect of 1,25-VitD3 on OGD/R-stimulated RN-C. In conclusion, 1,25-VitD3 protects neurons against CIRI through activating the antioxidant Nrf2/HO-1 pathway to restrain NLRP3-mediated pyroptosis.
Asunto(s)
Isquemia Encefálica , Daño por Reperfusión , Ratas , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/metabolismo , Piroptosis , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/farmacología , Vitamina D/metabolismo , Vitamina D/farmacología , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/farmacología , Transducción de Señal , Isquemia Encefálica/metabolismo , Estrés Oxidativo , Infarto de la Arteria Cerebral Media/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Oxígeno , Reperfusión , Neuronas/metabolismoRESUMEN
BACKGROUND: The antimicrobial effect of Magnolia officinalis extract (MOE) against Staphylococcus aureus was investigated in a minced mutton system and the mechanisms of its antimicrobial activity were studied by light microscopy, transmission electron microscopy and scanning electron microscopy observations. RESULTS: MOE inoculation effectively inhibited the growth of S. aureus in minced mutton compared with that in control meat without MOE. The cell membrane of S. aureus treated with MOE showed structural disorganisation and cytoplasmic volume overflow. After 48 h of exposure to MOE, many S. aureus cells had completely collapsed. CONCLUSION: The antimicrobial mechanisms of MOE resulted mainly in cell membrane and wall damage, causing increased permeability of cell membranes or lysis of cell walls and loss of cellular constituents, impairment of structural components and changes in bacterial cell morphology.
