Ward Jeremy L, Adams Sasha D, Delano Benjamin A, Clarke Caroline, Radhakrishnan Ravi S, Weisbrodt Norman W, Mercer David W
Department of Surgery, University of Texas Health Science Center, Houston, Texas 77030, USA.
J Trauma. 2010 Jan;68(1):69-75. doi: 10.1097/TA.0b013e3181a8b3a7.
Although ketamine has many beneficial effects in a rat model of noninfectious inflammation with lipopolysaccharide (LPS), its effects on gut ileus are unknown. We hypothesized that ketamine would improve LPS-induced ileus and therefore examined its effects on gastric emptying and intestinal transit as well as duodenogastric bile reflux and associated gastric bleeding.
Male rats received saline or ketamine (7 mg/kg ip) 1 hour before saline or LPS (20 mg/kg ip) for 5 hours. Thirty minutes before killing, rats received orogastric rhodamine B isothiocyanate-labeled dextran and 5 minutes later fluorescein isothiocyanate-labeled dextran via a duodenal catheter. GI contents were collected for dye, bile acid, and hemoglobin (index of bleeding) determinations.
LPS significantly impaired intestinal transit and increased duodenogastric bile reflux and gastric luminal hemoglobin content. Ketamine improved intestinal transit, prevented LPS-induced bile reflux, and diminished gastric bleeding. In mechanistic studies, ketamine also attenuated LPS-induced upregulation of the proinflammatory genes inducible nitric oxide synthase and cyclo-oxygenase-2 in the stomach but preserved expression of the anti-inflammatory gene heme-oxygenase-1 (Western blot).
These data suggest that ketamine may prevent LPS-induced gastric bleeding by decreasing bile reflux through improved intestinal transit or by local changes in nitric oxide, prostaglandin, and carbon monoxide metabolism.
尽管氯胺酮在脂多糖（LPS）诱导的非感染性炎症大鼠模型中具有多种有益作用，但其对肠道肠梗阻的影响尚不清楚。我们假设氯胺酮可改善LPS诱导的肠梗阻，因此研究了其对胃排空、肠道转运以及十二指肠-胃胆汁反流和相关胃出血的影响。
雄性大鼠在接受生理盐水或LPS（20mg/kg腹腔注射）前1小时接受生理盐水或氯胺酮（7mg/kg腹腔注射），持续5小时。在处死前30分钟，大鼠经口给予异硫氰酸罗丹明B标记的葡聚糖，5分钟后经十二指肠导管给予异硫氰酸荧光素标记的葡聚糖。收集胃肠道内容物用于染料、胆汁酸和血红蛋白（出血指标）测定。
LPS显著损害肠道转运，增加十二指肠-胃胆汁反流和胃腔内血红蛋白含量。氯胺酮改善肠道转运，预防LPS诱导的胆汁反流，并减少胃出血。在机制研究中，氯胺酮还减弱了LPS诱导的胃中促炎基因诱导型一氧化氮合酶和环氧化酶-2的上调，但保留了抗炎基因血红素加氧酶-1的表达（蛋白质印迹法）。
这些数据表明，氯胺酮可能通过改善肠道转运减少胆汁反流或通过一氧化氮、前列腺素和一氧化碳代谢的局部变化来预防LPS诱导的胃出血。
