右美托咪定对脓毒症大鼠认知功能障碍的保护作用

Protective Effect of Dexmedetomidine on Cognitive Dysfunction in Septic Rats

目的探讨右美托咪定对脓毒症大鼠认知功能障碍的影响。方法雄性SD大鼠60只,体质量250～300 g,采用随机数字表法将大鼠随机分为4组（n=15）：假手术组（A组）、假手术＋右美托咪定组（B组）、脓毒症组（C组）、脓毒症＋右美托咪定组（D组）。采用盲肠结扎穿孔法制备脓毒症模型。B、D组大鼠于假手术或盲肠结扎穿孔法后0、2、4、6 h腹腔注射右美托咪定10μg·kg-1,A、C组腹腔注射相应剂量的生理氯化钠溶液。给药后6、12、24、48 h,分别取大鼠尾静脉血1 ml,测定血清中炎症因子TNF-α和IL-1β水平。通过Y迷宫检测各组大鼠完成10次任务的正确率。结果与A组比较,C组大鼠术后1、3、5、7 d迷宫测试正确率均减少（P〈0.05）,血清中TNF-α和IL-1β水平升高（P〈0.05）;与C组比较,D组大鼠术后1、3、5、7 d迷宫测试正确率增加（P〈0.05）,血清中TNF-α和IL-1β水平降低（P〈0.05）。结论右美托咪定可明显减轻脓毒症大鼠认知功能损伤,其机制可能与降低炎症因子水平有关。

Objective To investigate the effect of dexmedetomidine （DEX） on cognitive dysfunction in septic rats. Methods Sixty male Sprague-Dawley rats （250 -300 g） were randomly divided into 4 groups： sham op- eration group （ group A）, sham operation ＋ DEX group （ group B）, sepsis group （ group C） and sepsis ＋ DEX group （group D）. Sepsis was produced by cecal ligation and puncture （CLP）. After CLP operation or sham opera- tion, animals in groups B and D were administered by intraperitoneal injection of 10 μg·kg-1 DEX at 0,2,4 and 6 hafter CLP or sham operation, and animals in groups A and C were administered by intraperitoneal injection of normal saline, respectively. Venous blood samples were drawn at 6,12,24,48 h after CLP or sham operation for the measurement of serum cytokines TNF- α and IL-1β. Animals in each group were tested to determine the proportion of 10 trials performed correctly using Y-maze food-reward method. Results Compared with group A, the correct rate by Y-maze food-reward method at 1,3,5,7 d after CLP operation was significantly decreased （P 〈 0.05 ）, while the concentrations of TNF- α and IL-1β in blood was significantly increased in group C （P 〈 0.05 ）. Compared with group C ,the correct rate by Y-maze food-reward method at 1,3,5,7 d after CLP operation was significantly in- creased（ P 〈0.05 ） ,but the concentrations of TNF- α and IL-1β in blood was significantly decreased in group D （ P 〈 0.05 ）. Conclusion DEX can alleviate cognitive dysfunction in septic rats by inhibiting the release of inflam- matory cytokines.