RESUMO
BACKGROUND: Dexmedetomidine has been reported to play an efficient role on multi-organ protection. Our study aims to investigate the neuroprotective of dexmedetomidine preconditioning on cerebral ischemic reperfusion (I/R) injury and investigate the underlining signaling mechanisms. METHODS: Cerebral I/R models were established with SD rats through middle cerebral artery occlusion (MCAO). After 2h of ischemia followed by 7days of reperfusion, the degree of cerebral tissue injury was detected by HE, Nissl and TUNEL staining. Glial fibrillary acidic protein (GFAP) positive and TNF-α positive cells were stained by immunohistochemistry and counted under microscope. TLR4, NF-κB and TIR-domain containing adapter-inducing interferon-ß (TRIF) expression were detected by real time PCR and western blot. RESULTS: Dexmedetomidine preconditioning markedly prevented the ischemia-induced cellular damage observed from HE and Nissl staining in hippocampus and cortex. Dexmedetomidine observably decreased the number of apoptotic cells in TUNEL staining. Besides, yohimbine could specifically suppress the protective effect of dexmedetomidine. GFAP expression was distinctly inhibited by dexmedetomidine preconditioning (10µg/kg, 20µg/kg) in cerebral ischemia area. Dexmedetomidine preconditioning inhibited the expression of TLR4 and NF-κB and increased that of TRIF. CONCLUSION: The results of this study suggest that dexmedetomidine preconditioning plays a neuroprotective role against I/R injury. Dexmedetomidine might suppress TLR4/NF-??B pathway and drive TLR4/TRIF signaling pathway to reduce the inflammatory injury.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Dexmedetomidina/farmacologia , Isquemia/tratamento farmacológico , NF-kappa B/metabolismo , Neuroproteção/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Isquemia Encefálica/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Interferon beta/metabolismo , Isquemia/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Under the guidance of chemical prescreening by direct infusion electrospray ionization mass spectrometry (DI ESI-MS), a new tetracyclic tetraterpenoid, methyl tortuoate D (1) was isolated from the soft coral Sarcophyton tortuosum collected from the South China Sea. Its structure and relative stereochemistry were established by MS, and 1D- and 2D-NMR spectroscopic techniques.