【摘要】 目的 观察氯胺酮对内毒素大鼠肺组织核因子-κB（NF-κB）活性的影响,探讨氯胺酮抑制炎性反应的机制。方法 成年大鼠24只随机分为四组（每组6只）,对照组,静脉注射生理盐水;内毒素（LPS）组,静脉注射内毒素8mg/kg+气管内注射内毒素100μg/kg;处理组（K4、K8组）,注射LPS后30min静脉分别注射氯胺酮4mg/kg或8mg/kg,随后每60min腹腔注射同等剂量氯胺酮。在注射生理盐水或LPS后240min开胸采集标本,用凝胶电泳迁移改变分析（EMSA）法检测肺组织NF-κB活性;同位素99mTc法测定肺血管通透性;并测血清中MDA和NO₂^-/NO₃^-浓度。结果 LPS组肺组织NF-κB活性较对照组明显升高,血中MDA和NO₂^-/NO₃^-浓度也较对照组明显增加;处理组肺组织NF-κB活性和血中NO₂^-/NO₃^-浓度较LPS组明显下降,与对照组比较差异无显著性。结论 氯胺酮能明显抑制内毒素诱导大鼠肺NF-κB活性,降低血中NO₂^-/NO₃^-含量,对内毒素所致肺损伤有保护作用。更多还原

【Abstract】 Objective To investigate the effect of ketamine on lipopolysaccharide ( LPS)-induced activation of nuclear factor-kappa B (NF-kB) in rat lung in vivo.Methods Twenty-four adult Wistar rats weighing 260-310 g were randomly divided into four groups with 6 animals in each group : (Ⅰ) control group received normal saline (NS) 0.3 ml iv;(Ⅱ) LPS group received LPS 8 mg·g-1 in 0.3 ml of NS iv + LPS 100μg·kg-1 in 0.2 ml of NS introduced into trachea;(Ⅲ) ketamine group A received ketamine 4 mg·kg-1 in 0.3 ml of NS iv 30 min after LPS + ketamine 4 mg·kg-1 ip after an interval of 60 min; (Ⅳ) ketamine group B received ketamine 8 mg·kg-1 iv and ip instead of 4 mg·kg-1 in groupⅢ. The animals were sacrificed 240 min after NS or LPS injection and chest was immediately opened. 10 ml of blood was removed from left heart for determination of MDA and NO2 / NO-3 concentration. The NF-kB activation of nuclear protein extracted from the lung was measured by EMSA. 99Tc was used to determine the pulmonary vascular permeability.Results NF-KB activation in the lung, serum MDA and N0-2 / NO-3 and the pulmonary vascular permeability were significantly increased in LPS group as compared with those in control group (P<0.05).Ketamine significantly reduced the NF-KB activation in the lung tissue and nitric oxide metabolic products N0-2 / NO-3 (P<0.05),but there was no significant difference in serum MDA content between LPS and the two ketamine groups. Conclusion Ketamine inhibits LPS-induced NF-KB activation in rat lung tissue, suggesting a possible mechanism of the reported lung-protective effects of ketamine during endotoxemia.更多还原