Propofol participates in gastric mucosal protection through inhibiting the toll-like receptor-4/nuclear factor kappa-B signaling pathway

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, 1 h 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 25 mg/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-kappa B)-in gastric mucosa, while suppressing the increased release of tumor neurosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) 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-kappa B-mediated inflammatory responses, and hamper apoptosis, which may contribute to its protective action against ethanol-induced gastric mucosal injury. (C) 2012 Elsevier Masson SAS. All rights reserved.