RESUMO
This study aimed to investigate the role of the Toll-like receptor 4 (TLR4) pathway in normal human gastric epithelial (GES-1) cells under hypoxia/reoxygenation (H/R) in vitro, and the effect of propofol on injured GES-1 cells as well as its possible mechanism. Before H/R induction, GES-1 cells were preconditioned with fat emulsion, propofol, or epigallocatechin gallate. Then cell viability, cell apoptosis, and related molecules in the cells were analyzed under experimental conditions. We found that propofol 50 µmol/L markedly inhibited the H/R injury under hypoxia 1.5 h/reoxygenation 2 hours by promoting GES-1 cell viability and decreasing cell apoptosis. The TLR4 signal may be involved in the protective effect of propofol against H/R injury. The malondialdehyde contents and superoxide dismutase activities were recovered under propofol preconditioning. In summary, propofol preconditioning may exert a protective effect on H/R injury in GES-1 cells and the mechanism may be via inhibition of the activated TLR4 signal under H/R conditions.
Assuntos
Células Epiteliais/metabolismo , Células Epiteliais/patologia , Oxigênio/farmacologia , Propofol/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/genética , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/enzimologia , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas I-kappa B/metabolismo , Malondialdeído/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Inibidor de NF-kappaB alfa , Necrose , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/genética , Superóxido Dismutase/metabolismo , Receptor 4 Toll-Like/genética , Fator de Transcrição RelA/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
AIMS: Propofol has demonstrated protective effects against digestive injury. Toll-like receptor-4 (TLR4) is involved in gastric mucosal injury. However, it has not yet been clarified whether propofol protects gastric mucosa from ethanol-induced injury and whether the mechanism involved is related to TLR4 activation. Therefore, this prospective study was carried out to address the issue. METHODS: Gastric mucosal injury was induced in mice by intragastric administration of ethanol. Propofol was given intraperitoneally 30 min before ethanol intragastric administration and, 1h later, gastric specimens were studied using hematoxylin--eosin staining, quantitative real-time RT-PCR, immunohistochemical staining and Western blot assays; serum specimens were studied using ELISA kits. RESULTS: Propofol at 25mg/kg significantly attenuated ethanol-induced gastric mucosal injury. In addition, propofol pretreatment significantly inhibited the upregulated expression of high-mobility group box-1 (HMGB1) protein, TLR4 and its downstream signaling molecules--myeloid differentiation factor 88 (MyD88) and nuclear factor kappa-B (NF-κB)--in gastric mucosa, while suppressing the increased release of tumor neurosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in serum. Furthermore, upregulation of the Bax/Bcl-2 ratio in gastric mucosa was clearly depressed by propofol. CONCLUSION: Propofol can inhibit HMGB1 expression and TLR4/MyD88/NF-κB-mediated inflammatory responses, and hamper apoptosis, which may contribute to its protective action against ethanol-induced gastric mucosal injury.