Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, 84, West Huaihai Road, Jiangsu Province 221002, Xuzhou, China.
Clin Res Hepatol Gastroenterol. 2013 Feb;37(1):e3-15. doi: 10.1016/j.clinre.2012.03.004. Epub 2012 Apr 17.
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.
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.
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.
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.
异丙酚已被证明具有对抗消化损伤的保护作用。Toll 样受体 4（TLR4）参与胃黏膜损伤。然而，目前尚不清楚异丙酚是否能保护胃黏膜免受乙醇诱导的损伤，以及所涉及的机制是否与 TLR4 激活有关。因此，进行了这项前瞻性研究。
通过胃内给予乙醇诱导小鼠胃黏膜损伤。在给予乙醇前 30 分钟，通过腹腔内给予异丙酚，1 小时后，使用苏木精-伊红染色、实时定量 RT-PCR、免疫组织化学染色和 Western blot 检测胃标本；使用 ELISA 试剂盒检测血清标本。
25mg/kg 的异丙酚可显著减轻乙醇诱导的胃黏膜损伤。此外，异丙酚预处理可显著抑制高迁移率族蛋白 1（HMGB1）蛋白、TLR4 及其下游信号分子髓样分化因子 88（MyD88）和核因子 kappa-B（NF-κB）在胃黏膜中的上调表达，同时抑制血清中肿瘤神经生长因子-α（TNF-α）和白细胞介素-1β（IL-1β）的增加释放。此外，异丙酚明显抑制胃黏膜中 Bax/Bcl-2 比值的上调。
异丙酚可抑制 HMGB1 表达和 TLR4/MyD88/NF-κB 介导的炎症反应，并抑制细胞凋亡，这可能有助于其对抗乙醇诱导的胃黏膜损伤的保护作用。
