title: The role of phosphoinositide-3-kinase/Akt pathway in propofol-induced postconditioning against focal cerebral ischemia-reperfusion injury in rats.
abstract: The aim of this study was to investigate whether propofol could provide postconditioning to ischemic brain injury and the role of phosphoinositide-3-kinase/Akt (PI3K/Akt) pathway in this phenomenon. Rats underwent 2 h of middle cerebral artery occlusion (MCAO) followed by 22 h of reperfusion were randomly divided into nine groups (n=15 each): sham-operated group, MCAO group, propofol 10, 20 and 35 mg x kg(-1) x h(-1) group (propofol 10, 20, 35 mg x kg(-1) x h(-1) infused at the onset of reperfusion for 30 min), wortmannin group (wortmannin 0.6 mg/kg administered 30 min before MCAO), and the other three groups received wortmannin followed by 10, 20 and 35 mg x kg(-1) x h(-1) propofol respectively. Propofol at doses of 10 and 20 mg x kg(-1) x h(-1) significantly reduced infarct volume, decreased neurological deficit scores and attenuated neuron apoptosis compared with MCAO group alone. Increased phosphorylated Akt (P-Akt) was observed in the ischemic penumbra of propofol 10 and 20 mg x kg(-1) x h(-1) group after transient MCAO. The selective PI3K inhibitor, wortmannin partly eliminated the neuroprotective effect and the elevation of P-Akt expression in ischemic penumbra induced by propofol. Propofol at dose of 35 mg x kg(-1) x h(-1) did not affect infarct volume, neurological deficit scores, neuronal apoptosis and the level of P-Akt in transient MCAO rats. Taken together, these results demonstrated that propofol at doses of 10 or 20 mg x kg(-1) x h(-1) infused at the onset of reperfusion for 30 min could provide neuroprotection to transient MCAO rats, and the postconditioning effect induced by propofol partly through maintaining the activity of PI3K/Akt pathway.
authors.affiliation: Department of Anesthesiology, General Hospital of Tianjin Medical University, Anshan Road No. 154, Heping District, Tianjin, 300052, China.
authors.forename: Hai-yun
authors.initials: HY
authors.lastname: Wang
authors.forename: Guo-lin
authors.initials: GL
authors.lastname: Wang
authors.forename: Yong-hao
authors.initials: YH
authors.lastname: Yu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D020520:Brain Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology / Q000627:therapeutic use; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology* / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D004791:Enzyme Inhibitors; D006993:Hypnotics and Sedatives; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin; D015742:Propofol