Role of PI3K-AMPA receptor subunit glutamate receptor 2 pathway in propofol postconditioning-induced reduction of cerebral ischemia-reperfusion injury in rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of phosphatidyl-inositol 3 kinase (PI3K)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit glutamate receptor 2 (GluR2) pathway in propofol postconditioning-induced reduction of cerebral ischemia-reperfusion (I/R) injury in rats.Methods One hundred and eighty male Sprague-Dawley rats,weighing 250-280 g,were randomly divided into 5 groups with 36 rats in each groupsham operation group (group S),I/R group,propofol postconditioning group (group P),intralipid postconditioning group (group Ⅰ),and PI3K inhibitor wortmannin + propofol postconditioning group (group W +P).The rats were anesthetized with intraperitoneal 10% chloral hydrate 350 mg/kg.Cerebral I/R was produced by 60 min middle cerebral artery occlusion followed by reperfusion.Propofol and 10% intralipid were infused via the femoral vein at a rate of 20 mg· kg-1· h-1 for 2 h starting from the onset of reperfusion in groups P and I,respectively,while the equal volume of normal saline was given instead in groups I/R and S.Wortmannin 0.6 mg/kg was injected intraperitoneally at 30 min before reperfusion in group W + P.The modified Neurological Severity Score (mNSS) was assessed and the cerebral infarct volume was detected at 12 and 24 h after operation.The hippocampi on the ischemic side were obtained at 4,6,12 and 24 h after operation for determination of expression of PI3KGluR2-containing AMPA receptor (by co-immunoprecipitation and Western blot) and activity of PI3K (by ELISA).Results Compared with group S,the mNSSs and infarct volume were significantly increased at 12 and 24 h after operation,and the activity of PI3K was decreased,and the expression of PI3K-GluR2-containing AMPA receptor was down-regulated at 4,6,12 and 24 h after operation in the other four groups (P ＜ 0.05).Compared with group I/R,the mNSSs and infarct volume were significantly decreased at 12 and 24 h after operation,and the activity of PI3K was increased,and the expression of PI3K-GluR2-containing AMPA receptor was up-regulated at 4,6,12 and 24 h after operation in group P (P ＜ 0.05).Compared with group W + P,no significant change was found in the parameters mentioned above in groups I/R and I (P ＞ 0.05),and the mNSSs and infarct volume were significantly decreased at 12 and 24 h after operation,and the activity of PI3K was increased,and the expression of PI3K-GluR2-containing AMPA receptor was up-regulated at 4,6,12 and 24 h after operation in group P (P ＜0.05).Conclusion PI3K-AMPA receptor subunit GluR2 pathway is involved in propofol postconditioning-induced reduction of cerebral I/R injury in rats.