氯胺酮可抑制内毒素诱导的肠道中核因子κB的激活及细胞因子的产生。
Ketamine suppresses endotoxin-induced NF-kappaB activation and cytokines production in the intestine.
作者信息
Sun J, Wang X D, Liu H, Xu J G
机构信息
Department of Anesthesiology, Jinling Hospital, College of Medicine, Nanjing University, Nanjing, China.
出版信息
Acta Anaesthesiol Scand. 2004 Mar;48(3):317-21. doi: 10.1111/j.0001-5172.2004.0312.x.
BACKGROUND
Ketamine has been advocated for anesthesia in endotoxemic and other severely ill patients because it is a cardiovascular stimulant. However, ketamine also suppresses serum levels of endotoxin-induced tumor necrosis factor-alpha, and reduces mortality in mice in endotoxin shock. Our study was designed to investigate the protective effect of ketamine on the endotoxin-induced proinflammatory cytokines and nuclear factor kappa B (NF-kappaB) activation in vivo.
METHODS
Adult male Wistar rats were randomly divided into six groups: saline controls; rats challenged with endotoxin (5 mg kg(-1)) and treated with saline; challenged with endotoxin (5 mg kg(-1)) and treated with ketamine (0.5 mg kg(-1)); challenged with endotoxin (5 mg kg(-1)) and treated with ketamine (5 mg kg(-1)); challenged with endotoxin (5 mg kg(-1)) and treated with ketamine (50 mg kg(-1)); and saline injected and treated with ketamine (50 mg kg(-1)). TNF-alpha, IL-6 and NF-kappaB were investigated in the tissues of the intestine (jejunum) after 1, 4 and 6 h.
RESULTS
Endotoxin caused transient production of TNF-alpha and IL-6 and activation of NF-kappaB in the intestine at peak times of 1, 4 and 1 h, respectively. Ketamine 0.5 mg kg(-1) suppressed endotoxin-induced TNF-alpha elevation and inhibited NF-kappaB activation in the intestine; a dose of 5 mg kg(-1) was required to inhibit IL-6.
CONCLUSION
Ketamine suppresses the production of proinflammatory cytokines such as TNF-alpha and IL-6 in the intestine, possibly via inhibition of NF-kappaB.
背景
氯胺酮因具有心血管兴奋作用，一直被推荐用于内毒素血症及其他重症患者的麻醉。然而，氯胺酮还可降低内毒素诱导的肿瘤坏死因子-α的血清水平，并降低内毒素休克小鼠的死亡率。我们的研究旨在探讨氯胺酮对内毒素诱导的体内促炎细胞因子及核因子κB（NF-κB）激活的保护作用。
方法
成年雄性Wistar大鼠随机分为六组：生理盐水对照组；用内毒素（5 mg kg⁻¹）攻击并用生理盐水处理的大鼠；用内毒素（5 mg kg⁻¹）攻击并用氯胺酮（0.5 mg kg⁻¹）处理的大鼠；用内毒素（5 mg kg⁻¹）攻击并用氯胺酮（5 mg kg⁻¹）处理的大鼠；用内毒素（5 mg kg⁻¹）攻击并用氯胺酮（50 mg kg⁻¹）处理的大鼠；注射生理盐水并用氯胺酮（50 mg kg⁻¹）处理的大鼠。分别在1、4和6小时后检测小肠（空肠）组织中的肿瘤坏死因子-α、白细胞介素-6和核因子κB。
结果
内毒素分别在1、4和1小时的峰值时间引起小肠中肿瘤坏死因子-α和白细胞介素-6的短暂产生及核因子κB的激活。0.5 mg kg⁻¹的氯胺酮可抑制内毒素诱导的小肠肿瘤坏死因子-α升高并抑制核因子κB的激活；抑制白细胞介素-6则需要5 mg kg⁻¹的剂量。
结论
氯胺酮可能通过抑制核因子κB来抑制小肠中肿瘤坏死因子-α和白细胞介素-6等促炎细胞因子的产生。
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