title: Propofol participates in gastric mucosal protection through inhibiting the toll-like receptor-4/nuclear factor kappa-B signaling pathway.
abstract: OBJECTIVE
  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-1β (IL-1β) in serum. Furthermore, upregulation of the Bax/Bcl-2 ratio in gastric mucosa was clearly depressed by propofol.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, 84, West Huaihai Road, Jiangsu Province 221002, Xuzhou, China.
authors.forename: Hui-Hui
authors.initials: HH
authors.lastname: Ye
authors.forename: Ke-Jian
authors.initials: KJ
authors.lastname: Wu
authors.forename: Su-Juan
authors.initials: SJ
authors.lastname: Fei
authors.forename: Xue-Wei
authors.initials: XW
authors.lastname: Zhang
authors.forename: He-Xia
authors.initials: HX
authors.lastname: Liu
authors.forename: Jiao-Li
authors.initials: JL
authors.lastname: Zhang
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects*; D006993:Hypnotics and Sedatives / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D015742:Propofol / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects*; D013272:Stomach Diseases / Q000139:chemically induced / Q000517:prevention & control*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors*
chemical_list: D006993:Hypnotics and Sedatives; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D000431:Ethanol; D015742:Propofol