Chinese Journal of Tissue Engineering Research ›› 2021, Vol. 25 ›› Issue (23): 3660-3665.doi: 10.12307/2021.036

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Sevoflurance combined with xenon pretreatment protects against spinal cord ischemia-reperfusion injury in a rat model

Fan Junchao, Chen Yong, Song Junjie   

  1. Department of Anesthesiology, The First Affiliated Hospital of Henan University, Kaifeng 475001, Henan Province, China
  • Received:2020-07-13 Revised:2020-07-15 Accepted:2020-08-15 Online:2021-08-18 Published:2021-01-26
  • Contact: Song Junjie, Master, Attending physician, Department of Anesthesiology, The First Affiliated Hospital of Henan University, Kaifeng 475001, Henan Province, China
  • About author:Fan Junchao, Master, Associate chief physician, Department of Anesthesiology, The First Affiliated Hospital of Henan University, Kaifeng 475001, Henan Province, China
  • Supported by:
    the Scientific and Technological Research Program of Henan Provincial Education Department, No. 19A320021 (to SJJ)

Abstract: BACKGROUND: Spinal cord ischemia-reperfusion injury is a serious nerve tissue injury. Both sevoflurane and xenon have been reported to have a certain protective effect on ischemia-reperfusion injury of viscersl organs, but whether the combination of the two can alleviate spinal cord injury is still unclear. 
OBJECTIVE: To study the protective effect and mechanism of sevoflurane combined with xenon pretreatment in the rats with spinal cord ischemia-reperfusion injury. 
METHODS: Sixty Sprague-Dawley rats were randomly divided into sham group, spinal cord ischemia-reperfusion group (IR), sevoflurane pretreated group (SI), xenon pretreated group (XI), sevoflurane and xenon pretreated group (SXI), PI3K inhibitor LY294002 group (SXI+LY), with 10 rats in each group. Sham group received sham operation, and the other groups received modeling operation for spinal cord ischemia-reperfusion injury. SI group, XI group, SXI group and SXI+LY group were pretreated with 3.4% sevoflurane, 50% xenon, combination of sevoflurane and xenon, sevoflurane combined with xenon and LY294002 (the inhibitor of PI3K) respectively. The hindlimb motor function of rats was evaluated using Basso, Beattie and Bresnahan (BBB) scores. Normal neurons and apoptosis of anterior horn cells in the spinal cord were detected by Nissl staining and TUNEL staining. The expression and phosphorylation levels of PI3K, AKT and cAMP-response element binding protein (CREB) in spinal cord tissue were detected by western blot. 
RESULTS AND CONCLUSION: The BBB scores for hindlimb motor function in the SI, XI and SXI groups were significantly higher than that in the IR group, and that of SXI group was significantly higher than that of SI group and XI group, while the BBB score in the SXI+LY group was significantly lower than that in the SXI group (all P < 0.001). Twenty-four hours after reperfusion, the apoptotic index of anterior horn cells in the SI group, XI group and SXI group was significantly lower than that in the IR group, that in the SXI group was significantly lower than that in the SI group and XI group, while that in the SXI+LY group was significantly higher than that in the SXI group (all P < 0.001). The expression of p-PI3K, p-AKT and p-CREB in spinal cord tissue was significantly increased in the SI group, XI group and SXI group as compared with the IR group, with a highest expression level in the SXI group, and the expression in the SXI+LY group was significantly lower than that in the SXI group (all P < 0.001). Therefore, pretreatment using sevoflurane combined with xenon has a better protective effect against spinal cord ischemia-reperfusion injury than using single drug, and the mechanism may be related to the effect on PI3K/AKT/CREB signaling pathway. 

Key words: sevoflurane, xenon, spinal cord, ischemia-reperfusion injury, PI3K/AKT/CREB signaling pathway, pretreatment

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