氯胺酮对内毒素血症大鼠炎性反应及血液动力学的影响  

Effects of ketamine on endotoxin-induced proinflammatory cytokine production and NF-κB activation in rat

作　　者：孙杰[1] 周志强[1] 段满林[1] 徐建国[1] 

机构地区：[1]南京军区总医院麻醉科

出　　处：《中华麻醉学杂志》2005年第3期187-189,共3页Chinese Journal of Anesthesiology

摘　　要：目的观察不同剂量氯胺酮对内毒素血症大鼠炎性反应及血液动力学的影响。方法36只成年雄性Wistar大鼠随机分为6组,每组6只,A组(对照组):静脉输注生理盐水10ml·kg-1·h-1;B组:静脉注射内毒素(LPS)5mg·kg-1,1min后静脉输注生理盐水10ml·kg-1·h-1;C组:静脉注射LPS5mg·kg-1,1min后静脉输注氯胺酮0.5mg·kg-1·h-1;D组:静脉注射LPS5mg·kg-1,1min后静脉输注氯胺酮5mg·kg-1·h-1;E组:静脉注射LPS5mg·kg-1,1min后静脉输注氯胺酮50mg·kg-1·h-1;F组:静脉输注氯胺酮50mg·kg-1·h-1。记录注射LPS后30、60、90、120min时平均动脉压(MAP)和心率(HR),并于注射LPS后120min时放血处死大鼠,测定外周血单核细胞(PBMC)中NF-κB含量及血浆肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)浓度。结果与基础值比较,B组注射LPS后MAP下降,HR增快,PBMC中NF-κB含量增加,血浆TNF-α、IL-6浓度升高。与B组比较,E、F组.MAP在注射LPS后120min升高,E组HR在注射LPS后90、120min、F组HR在注射LPS后60-120min降低,C、D、E组PBMC中NF-κB含量及血浆TNF-α浓度降低(P<0.05或0.01),但血浆IL-6浓度差异无统计学意义(P>0.05)。结论50mg·kg-1·h-1氯胺酮改善内毒血症大鼠血液动力学的紊乱,又可以在一定程度上抑制炎性反应,0.5。Objective To investigate the effects of ketamine on endotoxin-induced production of proinflammatory cytokines (IL-6, TNF-α) and activation of their modulating factor NF-κB in rat. Methods Thirty-six adult male Wistar rats weighing 250-300 g were randomly divided into 4 groups : (Ⅰ Ⅰ ) control group ( n = 6) ; (Ⅱ) endotoxin group received intravenous endotoxin ( Escherichia coli O111: B4)5mg·kg-1(n = 6); (Ⅲ) ketamine group received ketamine 50 mg·kg-1 · h-1 i.v. (n = 6) and (Ⅳ) endotoxin + ketamine group received ketamine 0.5 or 5 or 50 mg·kg-1 · h-1 after endotoxin ( n = 18 ) . The animals were anesthetized with urethane i. p. (1 g·kg-1) . Carotid artery was cannulated for BP and HR monitoring and jugular vein was cannulated for fluid or drug administration. Two hours after endotoxin administration the animals were sacrificed by exsanguination. Blood was collected and peripheral blood monocytes (PBMC) were isolated. NF-icB content in PBMC was measured by EMSA and plasma TNF-α and IL-6 concentrations were determined by ELISA. Results Progressive hypotension and tachycardia developed after endotoxin administration. Endotoxin also increased NF-icB content in PBMCs and plasma TNF-α and IL-6 concentrations. Ketamine 50 mg·kg-1 attenuated the endotoxin-induced hemodynamic response. Ketamine (0.5, 5, 50 mg·kg-1·h-1 ) suppressed NF-κB content in PBMC and inhibited plasma TNF-α level but plasma IL-6 level was not affected. Conclusion Ketamine can suppress endotoxin-induced NF-kappa B activation. Subanesthetic dose of ketamine has anti-inflammatory action.

关 键 词：血液动力学 内毒素血症 炎性反应 氯胺酮 肿瘤坏死因子-α(TNF-α) 大鼠 外周血单核细胞 血浆TNF-Α TNF-Α浓度 静脉输注 NF-κB 静脉注射 心率(HR) 10ml 生理盐水 PBMC LPS 平均动脉压 白细胞介素 不同剂量 0.05 内毒血症 

分 类 号：R96[医药卫生—药理学]