The Effects And Mechanisms Of Remifentanil Preconditioning On The Apoptosis Of Neural Cell In Rat Induced By Cerebral Ischemia-reperfusion

Objective To investigate the effects of Remifentanil preconditioning on the apoptosis of neural cell and the expression of Bcl-2 and Bax in rat cerebral tissue induced by cerebral ischemia-reperfusion.Methods A total of 54 adult Wistar rats,(female/male),weighting 200-250g were randomly divided into three groups(n=18):①sham operation group(Sham):performed by the same way of ischemia-reperfusion group except for ligating bilateral common carotid arteries.②ischemia-reperfusion group (IR):ligating bilateral common carotid arteries and receiving saline infusion intravenously in the same regime with those in Rem group.③Remifentanil preconditioning group(Rem):receiving remifentanil infusion intravenously at the rate of 1.2μg /kg/min in the regime (3×5 min infusion with 5 min interval) for 30 minutes before ischemic. An acute experimental forebrain ischemia Wistar rats model by ligating bilateral common carotid arteries for 30 minutes. The animals of sham group were killed at 6 h,12 h,24 h after operation and the animals of IRgroup and Rem group were killed at 6 h,12 h,24 h after reperfusion and left rat brain tissue was collected. Light microscopy was performed to verify the morphologic changes of cerebral cortex. The expression of Bcl-2 and Bax protein in cerebral cortex was detected with immunohistochemistry and MIAS-2000. The apoptosis index (AI)was measured by terminal deoxynucleotidy transferase mediated dUTP nick and labeling (TUNEL) method.Results①The result of light microscopy:The pathological lesion were lighter in Rem group than in IR group significantly(P<0.05).②AI were significantly lower in Rem group than in IRgroup at each point(P<0.05).③Bcl-2 protein optical density was significantly higher in Rem group than that in IR group at corresponding point(P<0.05), while Bax protein optical density were significantly lower in Rem group than in IR group at each time point(P<0.05), Bcl-2/Bax ratio in Rem group was higher than in IR group at each time point(P<0.05).④As reperfusion time prolonged, AI of neural cell in IR,Rem groups were increased,highest at hour 24(P<0.05)Conclusions①Apoptotic mechanism was involved in the cerebral ischemia/reperfusion injury,and the time of ischemia/reperfusion impacted the cell apoptosis.②Remifentanil preconditioning can significantly decrease the neuronal apoptosis of the cerebral I/R injury.③ The mechanism of protection may be related to induction of Bcl-2 protein expression and inhibition of Bax protein expression by Remifentanil preconditioning, thereby preventing neuronal apoptosis.