RESUMEN
AIMS: Autophagy has been regarded as a promising therapeutic target for spinal cord injury (SCI). Erythropoietin (EPO) has been demonstrated to exhibit neuroprotective effects in the central nervous system (CNS); however, the molecular mechanisms of its protection against SCI remain unknown. This study aims to investigate whether the neuroprotective effects of EPO on SCI are mediated by autophagy via AMP-activated protein kinase (AMPK) signaling pathways. METHODS: Functional assessment and Nissl staining were used to investigate the effects of EPO on SCI. Expressions of proteins were detected by Western blot and immunohistochemistry. RESULTS: Treatment with EPO significantly reduced the loss of motor neurons and improved the functional recovery following SCI. Erythropoietin significantly enhanced the SCI-induced autophagy through activating AMPK and inactivating mTOR signaling. The inhibitor of AMPK, compound C, could block the EPO-induced autophagy and beneficial action on SCI, whereas the activator of AMPK, metformin, could mimic the effects of EPO. In the in vitro studies, EPO enhanced the hypoxia-induced autophagy in an AMPK-dependent manner. CONCLUSIONS: The AMPK-dependent induction of autophagy contributes to the neuroprotection of EPO on SCI.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Autofagia/efectos de los fármacos , Eritropoyetina/uso terapéutico , Neuroprostanos/uso terapéutico , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/patología , Animales , Hipoxia de la Célula/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Glucosa/deficiencia , Locomoción/efectos de los fármacos , Masculino , Proteínas Asociadas a Microtúbulos/metabolismo , Células PC12 , Ratas , Ratas Sprague-Dawley , Recuperación de la Función/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: This study aimed to determine the relationship between intra-abdominal infection (IAI) and sarcopenia prospectively and to construct a nomogram to identify patients at a high risk of IAI. METHODS: We conducted a prospective study of 682 consecutive patients with gastric cancer who underwent radical gastrectomy. The sarcopenia elements, including lumbar skeletal muscle index, handgrip strength, and gait speed, were measured before surgery. Factors contributing to IAI were determined through univariate and multivariate analysis. A nomogram consisting of the independent risk factors was constructed to quantify the individual risk of IAI. RESULTS: Of the 682 patients enrolled in this study, 132 patients were diagnosed with sarcopenia and 61 were diagnosed with IAI. Logistic analysis revealed that sarcopenia, tumor size, pathological type, and multivisceral resection were independent prognostic factors for IAI. The nomogram model for IAI was able to reliably quantify the risk of IAI with a strong optimism-adjusted discrimination (concordance index, 0.736). CONCLUSIONS: Sarcopenia is an independent predictor of IAI. Our nomogram was a simple and practical instrument to quantify the individual risk of IAI and could be used to identify patients at a high risk.