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J Surg Res ; 248: 98-108, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31877436

RESUMO

BACKGROUND: This study aimed to investigate the role of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway in protection by peritoneal resuscitation (PR) using pyruvate-peritoneal dialysis solution (PY-PDS) against intestinal injury from hemorrhagic shock (HS) in rats. MATERIALS AND METHODS: Sixty-four rats were assigned to eight groups: group SHAM; group intravenous resuscitation (VR); groups NS, LA, and PY in which the rats were subjected to HS and PR with normal saline (NS), lactate-peritoneal dialysis solution (LA-PDS), and PY-PDS, respectively, combined with VR; and groups DMSO, RPM, and AG490 in which the rats were subjected to HS and VR with pretreatment of dimethyl sulfoxide (DMSO), rapamycin (RPM), and tyrphostin B42 (AG490). RESULTS: At 2 h after HS and resuscitation, the levels of diamine oxidase, 15-F2t-isoprostane, thromboxane B2, and endothelin-1, in the blood and the intestinal mucosal apoptotic index and caspase-3 were lower in groups PY, RPM, and AG490 than in groups VR, NS, LA, and DMSO. Group PY showed lower levels of malondialdehyde and myeloperoxidase and a higher level of superoxide dismutase than groups VR, NS, and LA. Phosphorylated JAK2 and phosphorylated STAT3 levels were lower in groups PY, RPM, AG490, and LA than in groups VR, NS, and DMSO. CONCLUSIONS: The protection mechanism of PR with PY-PDS combined with VR was related to the inhibition of the JAK/STAT signaling pathway during HS and resuscitation. The process might include suppression of oxidative stress, reduction of neutrophil infiltration, regulation of microcirculation, and inhibition of apoptosis.


Assuntos
Enteropatias/prevenção & controle , Ácido Pirúvico/uso terapêutico , Ressuscitação/métodos , Choque Hemorrágico/terapia , Animais , Soluções para Diálise , Avaliação Pré-Clínica de Medicamentos , Enteropatias/etiologia , Janus Quinases/antagonistas & inibidores , Janus Quinases/metabolismo , Masculino , Ácido Pirúvico/farmacologia , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição STAT/antagonistas & inibidores , Fatores de Transcrição STAT/metabolismo , Choque Hemorrágico/complicações , Transdução de Sinais/efeitos dos fármacos
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