氯胺酮对脓毒症大鼠肝细胞能量代谢的影响及其机制

Effect of ketamine on the energy metabolism of liver mitochondria in septic rats

目的:探讨氯胺酮对脓毒症大鼠肝线粒体的保护机制。方法:采用盲肠结扎穿孔(CLP)制作脓毒症模型,将大鼠随机分为假手术组(C组)、盐水组(NS组)、氯胺酮组(K组),模型制作12h开始分别给予盐水和氯胺酮,在给药前和给药4h后分别取静脉血,并在给药4h后制备肝线粒体和组织匀浆,分别采用Clark氧电极技术测定线粒体呼吸功能,ELISA法检测IL-1β和IL-6,分光光度法测定NO水平。结果:尽管K组的RCR和ADP/O明显低于C组,NO、给药前后IL-1β和IL-6水平明显皆高于C组;但与NS组比较,K组RCR和ADP/O升高,NO、给药4h后的IL-1β和IL-6水平降低。结论:氯胺酮能通过降低IL-1β和IL-6水平,减少肝组织NO的产生,保护线粒体呼吸功能。

Objective: To investigate the effect of ketamine on liver mitochondria in septic rats. Methods: Cecal ligation and puncture (CLP) were performed to make a sepsis model. 18 healthy rats were randomly divided equally into three groups: sham-operated group (C group), 0.9% physiological saline group (NS group) and ketamine group (K group). The drugs were given at 12 hours after the model was established. Blood samples were taken before and 4h after drugs. All rats were sacrificed after 4 hours of experiment and the livers were removed for measurement of observed parameters. The function of mitochondria was evaluated with the Clark oxygen electrode. The lever of IL-1β and IL-6 was assayed with ELISA. And the level of NO was measured. Results: Compared to the C group, the level of RCR , ADP/O decreased significantly and the level of NO , IL-1β, IL-6 increased both before and 4h after drugs in NS group. But in K group, the function of mitochondria was improved and the level of IL-1β,IL-6, NO was lower than that in NS group. Conclusion: Ketamine can protect the function of mitochondria in septic rats through decreasing the level of IL-1β, IL-6 and NO.