RESUMO
Daphnetin (7, 8-dihydroxycoumarin, DAPH), a coumarin derivative isolated from Daphne odora var., recently draws much more attention as a promising drug candidate to treat neuroinflammatory diseases due to its protective effects against neuroinflammation. However, itscontribution to chronic inflammatory pain is largely unknown. In the current work, we investigated the effects of DAPH in a murine model of inflammatory pain induced by complete Freund's adjuvant (CFA) and its possible underlying mechanisms. Our results showed that DAPH treatment significantly attenuated mechanical allodynia provoked by CFA. A profound inhibition of spinal glial activation, followed by attenuated expression levels of spinal pro-inflammatory cytokines, was observed in DAPH-treated inflammatory pain mice. Further study demonstrated that DAPH mediated negative regulation of spinal NF-κB pathway, as well as its preferential activation of Nrf2/HO-1 signaling pathway in inflammatory pain mice. This study, for the first time, indicated that DAPH might preventthe development of mechanical allodynia in mice with inflammatory pain. And more importantly, these data provide evidence for the potential application of DAPH in the treatment of chronic inflammatory pain.
Assuntos
Dor Crônica/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Dor/tratamento farmacológico , Umbeliferonas/farmacologia , Animais , Dor Crônica/imunologia , Dor Crônica/patologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Adjuvante de Freund/administração & dosagem , Adjuvante de Freund/imunologia , Heme Oxigenase-1/metabolismo , Humanos , Hiperalgesia/imunologia , Hiperalgesia/patologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Neuroglia/efeitos dos fármacos , Neuroglia/imunologia , Neuroglia/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Dor/imunologia , Dor/patologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologia , Medula Espinal/patologia , Umbeliferonas/uso terapêuticoRESUMO
We aimed to investigate the correlation between the Glasgow Coma Scale (GCS), the injury severity score (ISS) and serum levels of trace elements (TE) in severe trauma patients to analyze alteration of the levels of trace elements and serum biochemical indexes in the period of admission from 126 adult cases of severe brain trauma with traffic accidents. Multi-trace elements for patients in the trauma-TE groups were used. The results indicated that all patients presented an acute trace elements deficiency syndrome (ATEDs) after severe trauma, and the correlation between ISS and serum levels of Fe, Zn, and Mg was significant. Compared to the normal control group, levels of the trace elements in serum were significantly decreased after trauma, suggesting that enhancement of immunity to infection and multiple organ failure (MOF) via the monitoring and supplement of trace elements will be a good strategy to severe traumatic patients in clinics.
Assuntos
Cobre/sangue , Traumatismos Craniocerebrais/sangue , Ferro/sangue , Magnésio/sangue , Oligoelementos/sangue , Zinco/sangue , Adulto , Análise de Variância , Nitrogênio da Ureia Sanguínea , Traumatismos Craniocerebrais/diagnóstico , Creatinina/sangue , Feminino , Escala de Coma de Glasgow , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Espectrofotometria Atômica , Fatores de Tempo , Adulto JovemRESUMO
Neuropeptide Y (NPY) is one of the most important orexigenic agents in central regulation of feeding behavior, body weight and energy homeostasis in domestic chickens. To examine differences in the hypothalamic NPY between layer-type and meat-type of chickens, which are two divergent kinds of the domestic chickens in feeding behavior and body weight, we detected mRNA levels of NPY in hypothalamic infundibular nucleus (IN), paraventricular nucleus (PVN) and lateral hypothalamic area (LHA) of these two types of chickens using one-step real time RT-PCR. The meat-type chicken had more food daily (about 1.7 folds) and greater body weights (about 1.5 folds) and brain weights than the layer-type chicken at the age of 14 d. In the meat-type of chicken, NPY mRNA levels of the IN and PVN were significantly greater than those of the LHA, and were not significantly different between the IN and PVN. However, in the layer-type of chicken, NPY mRNA levels were significantly greater in the IN than those in the LHA and PVN, and were not significantly different between the PVN and LHA. In all these hypothalamic regions, the layer-type of chicken had significantly higher NPY mRNA levels than the meat-type chicken did. These results suggest the expression of NPY in the hypothalamus has a type-dependent pattern in domestic chickens.