氯胺酮对感染性休克大鼠保护作用的研究

Protective effect of ketamine against septic shock in rats

目的 观察氯胺酮对感染性休克大鼠血流动力学、血浆肿瘤坏死因子α( TNFα)和白细胞介素 6 ( IL 6 )水平的影响 ,探讨其可能的抗休克机制。方法 取健康成年雄性 ( SD)大鼠 2 0只 ,采用盲肠结扎加穿孔 ( CL P)法复制败血症或感染性休克模型。随机分为假 CL P组、CL P组、氯胺酮 组和氯胺酮 组。假CL P和 CL P组术前 30 m in经股静脉持续输注生理盐水 5 ml· kg- 1· h- 1 ,氯胺酮 和氯胺酮 组分别输注氯胺酮 5 m g· kg- 1· h- 1和 10 m g· kg- 1· h- 1。经股动脉穿刺置管 ,持续监测平均动脉压 ( MAP)、心率 ( HR)及采集血样 ,应用酶联免疫吸附试验 ( EL ISA)检测血浆 TNFα和 IL 6水平。结果 CL P组术后 MAP进行性下降 ,HR则先加快后减慢 ;血浆 TNFα和 IL 6水平明显升高。两种剂量的氯胺酮处理均能逆转 MAP和 HR下降 ,同时抑制血浆 TNFα和 IL 6水平升高 ,尤以氯胺酮 组作用更加明显。结论 氯胺酮对败血症或感染性休克大鼠具有明显的保护效应 。

Objective To investigate the effects and the mechanism of ketamine on hemodynamics and proinflammatory cytokine levels of plasma in septic shock rats. Methods Cecal ligation and puncture(CLP) was used to reproduce septic shock model. Twenty healthy and male SpragueDawlay(SD) rats weighing (225±25)g were randomly divided into four equal groups: sham CLP group, CLP group, ketamineⅠ (KTⅠ) and ketamineⅡ (KTⅡ) group. Thirty minutes before CLP, normal saline (0 9 %) was infused continously at a rate of 5 ml·kg -1 ·h -1 through the left femoral vein cannula in sham CLP and CLP group, and ketamine (5 mg·kg -1 ·h -1 and 10 mg·kg -1 ·h -1 , respectively) was infused continously in KTⅠ or KTⅡ group. The right femoral artery was cannulated to monitor mean arterial pressure. The plasma levels of tumor necrosis factorα(TNFα) and interleukin6(IL6) were measured using enzymelinked immunosorbent assays(ELISA). Results CLP produced progressive hypotension, and a large increase in the plasma TNFα and IL6 concentrations. The hemodynamic responses were reversed and the cytokine responses were suppressed in ketamine treated animals. Conclusion Ketamine administration has protective effect against septic shock in CLP rats.