Role of PTEN protein in sevoflurane postconditioning-induced mitigation of focal cerebral ischemia-reperfusion injury via activating PDK/Akt pathway in rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of phosphatase and tensin homolog deleted on ehromo-some ten (PTEN) protein in sevoflurane postconditioning-induced mitigation of focal cerebral ischemia-reperfusion (I/R) injury via activating PI3K/Akt pathway in rats.Methods One hundred and eight Sprague-Dawley rats,aged 2-3 months,weighing 250-280 g,were randomly assigned into 6 groups (n =18 each) using a random number tablesham operation group (group S),group I/R,I/R + sevoflurane postconditioning group (group I/R + S),I/R + normal saline group (group I/R + NS),I/R + selective PTEN inhibitor pic group (group I/R + P),and I/R + pic + sevofluraue postconditioning group (group I/R + P+ S).Focal cerebral I/R was induced by right middle cerebral artery occlusion (MCAO).The animals were anesthetized with intraperitoneal chloral hydrate.In I/R + P and I/R + P + S group,pic 20 μg/100 g (0.4 ml/100 g) was injected intraperitoneally every 3 h for 4 times before MCAO,and the equal volume of normal saline was given instead of pic in I/R + NS group.The rats in all sevoflurane postconditioning groups inhaled 2.5 ％ sevoflurane for 30 min starting from the onset of reperfusion,and the rats in the other groups inhaled oxygen for 30 min instead.At 24 h of reperfusion,neurological deficit scores (NDSs) were measured and the rats were then sacrificed.Their brains were removed for determination of infarct size (by TTC),cell apoptosis (by TUNEL),and expression of phosphorylated PTEN (p-PTEN) protein and phosphorylated Akt (p-Akt) (by Western blot).Apoptosis index was calculated.Results Compared with S group,the NDSs,percentage of cerebral infarct size and apoptosis index were significantly increased,and the expression of p-Akt and p-PTEN protein was up-regulated in the other 5 groups.Compared with I/R and I/R + NS groups,the NDSs,percentage of cerebral infarct size and apoptosis index were significantly decreased,and the expression of p-Akt and p-PTEN protein was up-regulated in I/R + S,I/R + P and I/R + P + S groups.There were no significant changes in the parameters mentioned above between I/R + S,I/R + P and I/R + P + S groups,and between I/R and I/R + NS groups.Conclusion Sevoflurane postconditioning can activate PI3K/Akt pathway via inhibiting PTEN protein,thus mitigating focal cerebral I/R injury in rats.