Therapeutic Effect And Mechanism Of Dexmedetomidine Postconditioning On Spinal Cord Ischemia-reperfusion Injury In Rabbits

[Objective]To study the role of dexmedetomidine postconditioning in the prevention of spinal cord ischemia-reperfusion injury（SCIRI）and its effect on neuronal apoptosis and inflammation of the spinal cord tissue.[Methods]Sixty white rabbits（adults）were equally and randomly divided into three groups（n=20）:Control group,ischemia-reperfusion injury group（I/R group）,dexmedetomidine postconditioning group（I/R+DEX group）.For the I/R group and I/R+DEX group,the abdominal aorta of the rabbits was clamped for 32 min to establish the model of SCIRI,while the rabbits in the Control group only undergoing arterial dissociation.Dex(10mg·kg^-1·h^-1)was administered intravenously at the beginning of reperfusion until 1 h later.Hind limb motor function of the rabbits was assessed using the modified Tarlov scale score at 12h,24h,and 48h after reperfusion.At 48h after reperfusion,the spinal cord tissue of animals was taken for related detection:neuronal apoptosis and histopathological changes were assessed by terminal deoxynucleotidyl transferase-mediated d UTP-biotin nick end labeling（TUNEL）staining and hematoxylin-eosin（HE）staining.The permeability of the blood-spinal cord barrier（BSCB）was evaluated by the trace method.The expression of JAK2,STAT3,p-JAK2,p-STAT3,Bcl-2,Bax,cleaved caspase-3,MMP-9,TNF-α,IL-6,and IL-1βwere detected by western blotting and RT-PCR.[Results]Compared with the Control group,I/R induced the reduction of the Tarlov score（P<0.05）,a rise of neuronal apoptosis rate（P<0.01）,an increase of EB content（P<0.01）and serious pathological injury of the spinal cord tissue.Meanwhile,I/R down-regulated the expression of Bcl-2（P<0.01）,and up-regulated the expression of Bax,cleaved caspase-3,MMP-9,TNF-α,IL-6 and IL-1β（P<0.01）.While compared with the I/R group,Dex significantly improved the Tarlov score（P<0.05 or P<0.01）,reduced neuronal apoptosis rate（P<0.01）,decreased EB content（P<0.01）and alleviated histological injury of the spinal cord tissue.Moreover,Dex up-regulated the expression of p-JAK2,p-STAT3 and Bcl-2（P<0.01）,and down-regulated the expression of Bax,cleaved caspase-3,MMP-9,TNF-α,IL-6 and IL-1β（P<0.01）.[Conclusions]Dexmedetomidine postconditioning can significantly alleviate SCIRI by activating the JAK2-STAT3-Bcl-2/Bax signaling pathway to inhibit neuronal apoptosis,and maintaining the structural integrity of BSCB to reduce the inflammatory response in the spinal cord tissue.