Effects of ketamine/xylazine on expression of tumor necrosis factor-α, inducible nitric oxide synthase, and cyclo-oxygenase-2 in rat gastric mucosa during endotoxemia
Effects of ketamine/xylazine on expression of tumor necrosis factor-α, inducible nitric oxide synthase, and cyclo-oxygenase-2 in rat gastric mucosa during endotoxemia
复制标题
DOI：
10.1097/01.shk.0000065766.72937.cf
复制
发表时间：
2003-07-01
期刊：
影响因子：
3.1
通讯作者：
Mercer, DW
中科院分区：
文献类型：
--
作者：
Helmer, KS;Cui, Y;Mercer, DW
一些麻醉剂减弱内毒素诱导的促炎基因的表达。氯胺酮/甲苯噻嗪 (K/X) 的麻醉组合可减少脂多糖 (LPS) 诱导的大鼠肝损伤。然而，K/X 对肠道功能和基因表达的影响尚不清楚。本研究的目的是检测 K/X 对 LPS 诱导的胃液积聚、胃肿瘤坏死因子 (TNF)-α、诱导型一氧化氮合酶 (iNOS) 和环氧合酶 (COX)-2 表达以及血清 TNF-α 蛋白水平随时间的影响。我们假设 K/X 会减弱这些 LPS 诱导的终点。大鼠腹腔内注射生理盐水或 K (70 mg/kg) 和 X (6 mg/kg)，然后再注射生理盐水或 LPS (20 mg/kg i.p.) 治疗 1、3 或 5 小时。收集血清、胃液和粘膜并测定TNF-α、iNOS和COX-2的表达。 LPS 在 1 小时内引起早期血清和胃粘膜 TNF-α 蛋白表达显着增加，K/X 预处理显着减弱了这种效应。与对照组相比，LPS 引起显着的胃瘀滞，并增加胃中 iNOS 和 COX-2 mRNA 表达以及 iNOS 蛋白表达。 K/X 可减弱 LPS 诱导的胃液积聚以及 iNOS mRNA 和蛋白质的上调，但不能减弱 COX-2。这些数据表明，在内毒素血症期间，K/X 抑制血清和胃中的一些促炎基因和病理生理反应。 K/X 的作用似乎抑制 iNOS 表达中的转录事件，这可能依赖于 K/X 诱导的早期 TNF-α 表达的抑制。此外，在内毒素血症大鼠模型中，尤其是评估胃的模型中，如果使用与氯胺酮和/或甲苯噻嗪联合麻醉，则需要仔细考虑，因为它们会改变 LPS 诱导的反应。
Some anesthetics attenuate expression of endotoxin-induced production of proinflammatory genes. The anesthetic combination of ketamine/xylazine (K/X) decreases lipopolysaccharide (LPS)-induced liver injury in rats. However, the effects of K/X on gut function and gene expression are unknown. The purpose of this study was to examine the effect of K/X on LPS-induced gastric fluid accumulation, and gastric tumor necrosis factor (TNF)-alpha, inducible nitric oxide synthase (iNOS), and cyclo-oxygenase (COX)-2 expression, as well as serum TNF-alpha protein levels over time. We hypothesized that K/X would attenuate these LPS-induced endpoints. Rats were given either intraperitoneal saline or K (70 mg/kg) and X (6 mg/kg) 1 h before saline or LPS (20 mg/kg i.p.) treatment of 1, 3, or 5 h. Serum and gastric fluid and mucosa were collected and TNF-alpha, iNOS, and COX-2 expression were determined. LPS caused a significant increase in early serum and gastric mucosal TNF-alpha protein expression at 1 h, an effect that was significantly attenuated by K/X pretreatment. LPS caused significant gastric stasis and increased iNOS and COX-2 mRNA expression and iNOS protein expression in the stomach when compared with controls. K/X attenuated LPS-induced gastric fluid accumulation and upregulation of iNOS mRNA and protein, but not COX-2. These data indicate that K/X inhibits some proinflammatory genes and pathophysiologic responses in the serum and stomach during endotoxemia. The effects of K/X appear to inhibit transcriptional events in iNOS expression, which may be dependent on K/X-induced inhibition of early TNF-alpha expression. Furthermore, in rat models of endotoxemia, especially those evaluating the stomach, careful consideration needs to be given if anesthetic combinations with ketamine and/or xylazine are used, as they alter LPS-induced responses.