Dexmedetomidine Pretreatment Attenuates The Neuroinflammation Induced By Cerebral Ischemia-reperfusion

Objective To observe the protective effect of dexmedetomidine(DEX)after a middle cerebral artery occlusion(MCAO)in rats and to observe the mechanism of dexmedetomidine(DEX)pretreatment alleviates inflammation after a middle cerebral artery occlusion(MCAO)in rats in this study,.Methods 1.Eighty-four male Sprague-Dawley rats,weighting 220-250 g,were assigned into seven experimental groups,6 in each group.group S(Sham-operation group): rats only received the carotid artery of one side isolation,group M(group MCAO): the blood flow of one side of middle cerebral carotid artery was blocked for 90 minutes,group D10(dexmedetomidine 10 ug/kg,intraperitoneal injection 30 min before MCAO),group D50(dexmedetomidine 50 ug/kg,intraperitoneal injection 30 min before MCAO),group D100(dexmedetomidine 100 ug/kg,intraperitoneal injection 30 min before MCAO),group DY(yohimbine 5 mg/kg,10 min before dexmedetomidine 50 ug/kg administrated),group Y(yohimbine 5 mg/kg,intraperitoneal injection 40 min before MCAO).2.The degree of brain injury was assessed by neuro-functional assessment in rats of group S,group M,group D10,group D50,group D100,group DY and group Y.3.After the establishment of the model of middle cerebral artery occlusion in rats,the brain tissue of rats was taken 24 h after reperfusion,and the area of cerebral infarction was measured by TTC staining,and the volume of cerebral infarction of each group was calculated according to the formula.4.After the establishment of the MCAO model,brain tissue was taken from rats 24 h after reperfusion and the apoptosis of neurons in the cerebral cortex of the seven groups was assessed by TUNEL double staining.5.Enzyme linked immunosorbent assay(ELISA)was used to determine the levels of inflammatory cytokines tumor necrosis factor(TNF-?)and interleukin(IL-1?)in the ischemic brain tissue of the seven groups.6.Western blot was used to investigate the contents of AMPK and phosphorylated AMPK(p AMPK)in ischemia cortex of seven groups of rats,and the expression ratio of p AMPK/AMPK was calculated.7.After ischemia reperfusion for 1,2 and 5 days,the motor function of seven groups of rats was evaluated according to the climbing board experiment,balance beam experiment and suspension test.Results 1.Compared with the group M,the neural function score of group D10,group D50 and group D100 was significantly reduced(P < 0.01),and the decrease was more obvious in the group D50 and group D100(P < 0.05).Compared with the group D50,the neurological function score of group DY was significantly increased(P < 0.01)2.Compared with the group M,cerebral infarction volume was significantly reduced in the group D10,group D50 and group D100(P < 0.01),and the decrease was more significant in the group D50 and group D100(P < 0.05).Compared with the group D50,the cerebral infarction volume of group DY was significantly increased(P < 0.01).3.Compared with the group M,the number of apoptotic neurons was significantly reduced in the group D10,group D50 and group D100(P < 0.01),and the decrease was more obvious in the group D50 and group D100(P < 0.05).Compared with group D50,the number of apoptotic neurons in group DY was significantly increased(P < 0.01).4.Compared with the group M,the levels of inflammatory cytokines tumor necrosis factor(TNF-?)and interleukin(IL-1?)in brain tissues were significantly decreased in group D10,group D50 and group D100(P < 0.01),and the decrease was more obvious in group D50 and group D100(P < 0.05).Compared with the group D50,the levels of inflammatory cytokines tumor necrosis factor(TNF-?)and interleukin(IL-1?)in brain tissues were significantly increased in the group DY(P < 0.05).5.Compared with the group M,the expression ratio of p AMPK/AMPK was significantly increased in the group D10,group D50 and group D100(P < 0.01),and the increase was more obvious in group D50 and group D100(P < 0.05).Compared with the group D50,the expression ratio of p AMPK/AMPK was significantly decreased in the group DY(P < 0.01).6.Compared with the group M,the motor function score was significantly increased in the group D10,group D50 and group D100(P < 0.05),and the increase was more obvious in the group D50 and group D100(P < 0.05).Compared with the group D50,the motor function score of group DY was significantly reduced(P < 0.05).Conclusion These findings suggest that precondition of dexmedetomidine exerted anti-inflammatory effects after MCAO,and the activation of AMPK may involve in the mechanism.