盐酸氯胺酮注射液对脓毒症大鼠炎症介质及生存率的影响

Effects of Ketamine on Survival Rate and Serum Concentration of Tumor Necrosis Factor-α,Interleukin-6 in Septic Rats

目的探讨氯胺酮在盲肠结扎穿孔术(CLP)脓毒症大鼠中对炎性介质及生存率的影响。方法将132只雄性 SD大鼠随机分为3组:①正常对照组,②对照组,③氯胺酮组。每组各分为Ⅰ、Ⅱ、Ⅲ、Ⅳ等4个亚组。对照组和氯胺酮组建立 CLP脓毒症模型。术毕30 min 开始给药,氯胺酮组经肌肉注射氨胺酮50 mg/kg,q12h;正常对照组与对照组则给予等容积的生理盐水,直至大鼠死亡或5 d 观察期结束。每组的Ⅰ亚组大鼠观察5 d 的生存情况;Ⅱ、Ⅲ、Ⅳ亚组的大鼠分别手术前0 h,术后4 h 以及对照组的Ⅳ亚组各只大鼠的临终时刻为观察时间,分别处死每组中一个亚组的大鼠测定血中肿瘤坏死因子(TNF-α)白介素-6(IL-6)的水平。结果与对照组相比,氯胺酮组的5 d 生存率明显为高(P<0.01),且氯胺酮组 TNF-α和 IL-6的血清水平在 CLP 术后4h 及临终时点均较对照组明显降低(P<0.01)。结论氯胺酮能够抑制 CLP 脓毒症大鼠血清 TNF-α、IL-6水平,从而提高大鼠的生存率。

Objective To observe the effects of ketamine on survival rate and serum concentration of tumor necrosis factor-α（ TNF--α）, interleukin-6 （IL-6） in septic rats after ligature of cecum and to investigate the possibe mechanism. Methods 132 male SD rats were randomly allocated into 3 groups：①Normal control group ,② Control group ,③Ketamine group. Each group was again divided into 4 subgroup（ Ⅰ , Ⅱ , Ⅲ, Ⅳ ） . A cecum ligation and puncture procedure was used to male septic rats model. After half an hour of operation. Ketamine group was administed with ketamine 50 mg/kg every 12 hours imtramuscularly, whereas normal control group and control group were given equivalent volume normal saline until rats died or 5 days observation ended. The survival period was observed in each subgroups Ⅱ , Ⅲ, Ⅳ for measurement of TNF-α. IL-6 at 0 hour before operation ,4 hours after operation hnd the dying point of each rag of control subgroup Ⅳ. Results Decrease in the levels of TNF-α and IL-6 were found at anytime after ketamlne intervention （ P 〈 0.01 ）. The 5 days survival rute：a significantly higher survival rate was found in ketamine group than in control group （ P 〈 0.01 ）. Conclusion Ketamine could restrain the TNF-α, IL-6 by the CLP（ cecamhigature procedure）and rose the survival rate of rats with sepsis.