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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