Protective Effect Of Dexmedetomidine On Brain Injury After Cardiopulmonary Resuscitation In Rats

Background: Brain damage after cardiopulmonary resuscitation is one of the leading causes of disability and death in patients with cardiac arrest.Due to the unique vulnerability of the brain,its tolerance to ischemia/reperfusion injury is extremely limited.Therefore,ischemic brain injury is still an important factor in the poor prognosis after cardiac arrest.Its pathophysiology mainly includes two aspects : cell homeostasis imbalance promotes apoptosis after ischemic and pro-inflammatory response after reperfusion.Dexmedetomidine has been shown to have neuroprotective effects and can alleviate brain damage,but its protective effect on brain damage after cardiopulmonary resuscitation is unclear.Objective: This study is to investigate the effect of dexmedetomidine post-treatment on brain function after cardiopulmonary resuscitation in rats and its possible mechanism.Methods:In this study,a rat cardiac arrest-cardiopulmonary resuscitation model was prepared by using end-tidal clamped tracheal catheter combined with intravenous cis-atracurium to simulate asphyxia.Thirty male Sprague-Dawley rats were randomly divided into 3 groups: sham operation group(Sham group,n=6),control group(Control group,n=12),dexmedetomidine post-treatment group(Dex group,n =12);Sham group only underwent tracheal intubation and arteriovenous puncture,Control group and Dex group for 6 min asphyxia model;Dex group rats with autologous circulation after reinjection with microinjection pump 25 ?g/kg hydrochloric acid right Metoprolidine injection,the Control group was infused with the same amount of normal saline after spontaneous circulation recovery.The neurological deficits were scored at 24 h,48h and72 h after spontaneous circulation recovery.The rats were tested at 5d.The ELISA method was used to detect IL-1? in serum of each group at 2h,24 h and 48 h.The expression level of TNF-? was detected.After 5 days of spontaneous circulation recovery,the rat cortex was taken.The apoptosis index of brain cells was calculated by Tunel staining.The expression of Caspase-3 and NF-?B in the cortex of each group was detected by Western Blot.Results:1.Compared with the Control group,the cumulative survival rate of the Dex group was significantly increased within five days after cardiopulmonaryresuscitation,with a 5-day cumulative survival rate of 50% in the Control group and66.7% in the Dex group;2.At 24 h,48h,72 h after restoration of spontaneous circulation,the Geocadin neurological deficit score was scored in rats.The results showed that compared with the Sham group,the neurological deficit scores of the Control group decreased at each time point(p<0.01).However,compared with the Control group,the Dex group of the functional defect scores were increased at each time point(p<0.05).3.The results of the rotating rod test showed that the crawling time,crawling distance and average speed of the Dex group were higher than the Control group(p<0.05).There was no significant difference between the Dex group and the Sham group.4.Compared with the Control group,the serum levels of TNF-? at 2h in the Dex group were significantly lower(p<0.05),and there was no significant difference between the 24 h and 48 h groups.There was no significant difference between the Dex group and the Sham group.5.Compared with the Control group,the expression of IL-1? in the serum of the Dex group at 2h,24 h and 48 h was significantly decreased(p<0.05),while the Dex group and There was no significant difference in the Sham group;6.Compared with the Control group,the Dex group was compared with the Control group.The apoptotic index induced by cardiac arrest/cardiopulmonary resuscitation was significantly lower(p<0.001),while there was no significant difference between the Dex group and the Sham group.7.Compared with the Control group,Caspase-3 was found in the brain tissue of the Dex group.There was a significant decrease in expression(p<0.05),while there was no statistical difference between the Dex group and the Sham group.8.Compared with the Control group,the expression of NF-?B in the brain tissue of the Dex group was significantly reduced(p<0.05),while the Dex group and the Sham group were not statistically different.Conclusion: Post-treatment with dexmedetomidine can reduce brain cell apoptosis after cardiopulmonary resuscitation in rats,reduce central nervous system inflammation,improve survival rate,neurological function score and exercise injury after spontaneous circulation recovery in rats,and alleviate cardiopulmonary resuscitation in rats.Brain damage.