Role of PI3K-AMPA receptor subunit glutamate receptor 2 pathway in propofol postconditioning-induced reduction of cerebral ischemia-reperfusion injury in rats

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 group： sham operation group （group S）, I/R group, propofol postconditioning group （group P）, intralipid posteonditioning 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, respec- tively, while the equal volume of normal saline was given instead in groups I/R and S. Wortmannin 0.6 mg/kg wasinjected 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 ischemie side were obtained at 4, 6, 12 and 24 h after operation for determination of expression of PI3K- GluR2-containing AMPA receptor （by co-immunopreeipitation 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-eontaining AMPA re- ceptor 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 posteonditioning-indueed reduction of cerebral I/R injury in rats. Key words: 1-phosphatidylinositol 3- kinase ; Receptors, AMPA ; Propofol ; Reperfusion injury ; Brain ; Postconditioning