Posttreatment With LYRM03 Protects Rats From Acute Lung Inflammation Induced by Lipopolysaccharide via Suppressing the NF-κB/MyD88/TLR4 Axis.
J Surg Res
; 243: 316-324, 2019 11.
Article
en En
| MEDLINE
| ID: mdl-31255931
ABSTRACT
BACKGROUND:
3-amino-2-hydroxy-4-phenyl-valyl-isoleucine (LYRM03) has been shown to be beneficial in a rat model of acute lung injury (ALI). Nonetheless, the pharmacologic action of LYRM03 interference has not been demonstrated to occur through oxidative stress and apoptosis in a rat lipopolysaccharide (LPS)-induced ALI model, and the potential pathogenic mechanism needs to be clarified. Our research intended to explore the mechanism of action using an in vivo rat LPS-induced ALI model and highlight the associated pathogenesis.METHODS:
Sprague-Dawley rats were randomly assigned to the following five groups Sham; LPS (5 mg/kg); LPS + LYRM03 (5 mg/kg); LPS + LYRM03 (10 mg/kg); and LPS + LYRM03 (20 mg/kg). Pulmonary injury indicators were documented at 24 h after LPS-induced ALI. Morphologic alterations, such as the extent of the injury, were determined using hematoxylin-eosin staining. Furthermore, expression levels of oxidative stress indicators (malondialdehyde, superoxide dismutase, and glutathione peroxidase) and inflammatory molecules (tumor necrosis factor-α, interleukin-8, and interleukin-6) in circulation were observed. The production of apoptosis-associated proteins (poly ADP-ribose polymerase, c-caspase 3, B-cell lymphoma-2, and Bcl2 associated X), inflammatory mediators (high mobility group box-1, toll-like receptor 4, nuclear factor-kappa B p65, and myeloid differentiation primary response 88), and inhibitor of kappa B-α were determined through Western blotting. Real-time polymerase chain reaction was applied to assess the messenger RNA expression of the inflammatory mediators.RESULTS:
The LPS-treated group exhibited a remarkable increase in the extent of the pulmonary injury, oxidative stress indicator secretion, inflammatory molecule release, and inflammatory mediator production and an increase in the inhibitor of kappa B-α levels relative to the Sham group. The LYRM03 (5 and 10 mg/kg)-treated groups exhibited a remarkable decrease relative to the LPS group. In addition, treatment with LYRM03 (20 mg/kg) powerfully limited the extent of the injury and demonstrated anti-inflammatory actions.CONCLUSIONS:
The results of this investigation indicated that treatment with LYRM03 plays a role in lung defense by inhibiting the NF-κB/MyD88/TLR4 pathway.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Oligopéptidos
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FN-kappa B
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Receptor Toll-Like 4
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Factor 88 de Diferenciación Mieloide
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Lesión Pulmonar Aguda
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Surg Res
Año:
2019
Tipo del documento:
Article
País de afiliación:
China