目的: 用动物实验,分析右美托咪啶复合舒芬太尼对大鼠镇静、呼吸抑制的影响,并探讨药物具体作 用机制。方法: 收集 80 只健康 SD 雄性大鼠,翻正反射实验分组为实验组 1、实验组 2、实验组 3,镇静实验 分组为实验组 4、实验组 5、实验组 6,肺功能实验、及磷脂酰肌醇 3 激酶（PI3K）、蛋白激酶 B（Akt）、磷酸化 Akt（p-Akt）蛋白相对表达量检测分组为对照组、实验组 7、实验组 8、实验组 9,液相色谱 - 串联质谱（LC- MS/MS）实验分组为实验组 10、实验组 11、实验组 12。实验组 1、4、7、10 以 20.0 µg·kg-1 舒芬太尼尾静脉 注射,实验组 2、5、8、11 以 25.2 µg·kg-1 右美托咪啶尾静脉注射,实验组 3、6、9、12 以 20.0 µg·kg-1 舒芬太 尼联合 25.2 µg·kg-1 右美托咪啶尾静脉注射,对照组以等量生理盐水尾静脉注射。结果: 翻正反射实验中, 与实验组 1 比较,实验组 2 诱导时间增加,实验组 3 诱导时间减少（P<0.05）;与实验组 2 比较,实验组 3 诱导时间减少（P<0.05）;与实验组 1 比较,实验组 2、实验组 3 持续时间延长（P<0.05）;与实验组 2 比较,实 验组 3 持续时间延长（P<0.05）。给药 30、40 min 时,实验组 4、实验组 5、实验组 6 镇静效果评分升高,但实 验组 6 较实验组 4、实验组 5 低。与实验组 7 比较,实验组 8、实验组 9 RF、TV、MV 变化率降低,呼吸抑制 发生时间较慢,持续时间延长,PI3K、p-Akt、p-Akt/Akt 蛋白相对表达量升高（P<0.05）;与实验组 8 比较,实 验组 9 呼吸抑制持续时间延长,PI3K、p-Akt、p-Akt/Akt 蛋白相对表达量升高（P<0.05）。给药 5、15 min 时, 与实验组 10 比较,实验组 12 舒芬太尼血浆、脑组织浓度及 Kp 值降低（P<0.05）。给药 5、15 min 时,与实验 组 11 比较,实验组 12 右美托咪啶血浆浓度降低,脑组织浓度、Kp 值升高（P<0.05）。结论: 右美托咪啶复合 舒芬太尼可延长大鼠镇静时间、呼吸抑制持续时间,机制可能与激活 PI3K/Akt 通路有关。
Objective: To study the effects of dexmedetomidine and sufentanil on the sedation and respiratory inhibition of rats and to explore the specific mechanism of the drug using animal experiment. Methods: Eightyhealthy male SD rats were divided into experimental group 1,2 and 3,sedation group 4,5 and 6. Lung function test and relative expression of phosphatidylinositol 3 kinase（PI3K）,protein kinase B（Akt）and phosphorylated Akt（p-Akt）protein were detected and divided into control group,experimental group 7, experimental group 8 and experimental group 9. Liquid chromatography tandem mass spectrometry（LC- MS/MS）experiments was divided into experimental group 10,experimental group 11 and experimental group 12. Sufentanil（20.0 μg·kg-1）was injected into the tail vein of experimental group 1,4,7 and 10,dexmedetomidine （25.2 μg·kg-1）was injected in experimental group 2,5,8 and 11,and 20.0 μg·kg-1 sufentanil combined with 25.2 μg·kg-1 dexmedetomidine were injected in experimental group 3,6,9 and 12. The control group was injected with equal amount of physiological saline. Results: In the righting reflex experiment,compared with group 1,the induction time of group 2 was increased,while that of group 3 was decreased（P<0.05）. Compared with group 2,the induction time of group 3 was decreased（P<0.05）. Compared with experimental group 1,the duration of experimental group 2 and group 3 was prolonged（P<0.05）. Compared with group 2,the duration of group 3 was prolonged（P<0.05）. At 30 min and 40 min after administration,the sedative effect scores of experimental group 4, 5 and 6 increased,but the sedative effect score of experimental group 6 was lower than that of experimental group 4 and 5. Compared with experimental group 7,the change rate of RF,TV and MV in experimental group 8 and 9 decreased,the occurrence time of respiratory depression was slower,the duration of respiratory depression was prolonged,and the relative expression of PI3K,p-Akt and p-Akt/Akt protein was increased（P<0.05）. Compared with experimental group 8,the duration of respiratory depression in experimental group 9 was prolonged,and the relative expression of PI3K,p-Akt and p-Akt/Akt protein was increased（P<0.05）. At 5 min and 15 min after administration,the concentrations of sufentanil in plasma and brain tissue and KP value in experimental group 12 were lower than those in experimental group 10（P<0.05）. At 5 min and 15 min after administration,the plasma concentration of dexmedetomidine in the experimental group 12 was lower than that in the experimental group 11,while the brain tissue concentration and KP value were increased（P<0.05）. Conclusion: Dexmedetomidine combined with sufentanil can prolong the sedation time and the duration of respiratory depression in rats. The mechanism may be related to the activation of PI3K/Akt pathway.
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