氯胺酮对心肌缺血/再灌注大鼠心肌NF-κB和血清白细胞介素6的影响

Effects of ketamine on myocardial NF-kappa B expression and serum IL-6 level following myocardial Ischemia-reperfusion in rats

目的 观察氯胺酮对心肌缺血/再灌注(I/R)大鼠心肌NF-κB和血清白细胞介素6(IL-6)的影响。方法健康SD大鼠24只,随机分为4组,每组6只,假手术组(A组),I/R组(B组),I/R+氯胺酮5mg·kg-1组(C组),I/R+氯胺酮10 mg·kg-1组(D组)。大鼠心肌缺血30 min,再灌120 min后,取心肌组织用Western-blot法检测心肌细胞核NF-κB的含量。分别于再灌注30、120 min时,取左颈内静脉血,采用ELISA法检测血清IL-6浓度。结果B、C、D组心肌细胞核NF-κB含量均高于A组,升高程度依次下降(P<0.05或0.01),各组两个时间点血清IL-6浓度也高于A组,升高程度也依次下降(P<0.01或0.05)。结论氯胺酮能抑制心肌I/R大鼠心肌NF-κB表达及IL-6的释放,抑制I/R引起的心肌炎性反应。

Objective Ketamine has been shown to suppress pro-inflammatory cytokines like TNF-α and IL-6. The purpose of this study was to investigate the effects of ketamine on myocardial NF-κB expression and serum IL-6 level in a rat model of myocardial ischemia-reperfusion (I/R) .Methods Twenty-four healthy male SD rats aged 4-8 months weighing 200-250 g were randomly divided into four groups with 6 animals in each group : (A)control group; (B) I/R group; (C) ketamine 5 mg· kg-1 +I/R(I/R+K1) and (D) ketamine 10mg·kg-1 + I/R (I/R + K2) . The animals were anesthetized with intraperitoneal 10% chloral hydrate 40 mg·kg-1. Chest was opened and heart exposed. Left coronary artery was temporarily occluded at 1 mm inferior to left auricle for 30 min followed by 120 min reperfusion. Myocardial ischemia was confirmed by decoloration of apex and elevation of S-T segment. In control group (A) heart was exposed but left coronary artery was not occluded. In group C and D ketamine 5 mg·kg-1 or 10mg·kg-1 was given i.v. during ischemia. The animals were sacrificed at the end of 120 min reperfusion. A piece of myocardium (0.1 g) was obtained from apex for determination of myocardial NF-κB expression (Western-blot) . Blood samples were taken at 30 min and 120 min of reperfusion for determination of serum IL-6 level (ELISA) .Results The serum IL-6 level at 30 min and 120 min of reperfusion and myocardial NF-κB expression were significantly increased in I/R group (B) compared with those in control group ( P < 0.01) . Ketamine administration reduced the increase in serum IL-6 level and myocardial NF-κB expression induced by I/R in a dose-dependent manner (P < 0.05 or 0.01) .Conclusion Ketamine suppresses myocardial NF-κB expression and serum IL-6 level and inflammatory response induced by myocardial I/R.