Expression Of PI3K/Akt/mTOR/S6K1Signaling Pathway After Cerebral Ischemic-Reperfusion And Atorvastatin Intervention In SD Rats

Objective:To study the expression of AKT/P-AK and S6K1/P-S6K1in brain contex following cerebral ischemia/reperfusion and intervention of atorvastatin in SD rats, and to probe the possible role of PI3K/Akt/mTOR/S6K1Signaling Pathway in cerebral ischemia/reperfusion and the possible protective mechanism of atorvastatin intervention.Methods:52healthy male SD rats were randomly divided into four groups: normal group, sham operation group, ischemia/reperfusion group and atorvastatin intervention group. The middle cerebral artery occlusion was used to perform the rat cerebral ischemic-reperfusion injury model. Nothing was done in normal group and sham operation group, in ischemia reperfusion group, we administrated stomach with physiological saline only; but in intervention group, the animals were lumbar injected by atorvastatin (10mg/kg) at Oh,24h and48h after reperfusion. All rats were killed after72h reperfusion. The neurological deficit score was performed by another investigator, and the brains were preserved with different methods for TTC staining, HE staining and TUNEL staining; The protein expression of Akt、P-Akt、S6K1and P-S6Klin each group was investigated by Western blotting. Results of data were analyzed by statistic soft package of Spss19.0.Results:1. After cerebral ischemia/reperfusion, TTC staining showed the volume of infarct area in intervention group was significantly diminution than those in ischemia-reperfusion group(11.48±4.79%,21.31±5.45%).2. TUNEL staining in normal group and sham operation group only showed a very small number of TUNEL-positive cells (1.02±0.76vs.2.1±0.83). The number of TUNEL-positive cells in model group was obviously higher than those in normal group or sham operation group (P<0.001); but in intervention group, the apoptotic cell was reduced significantly compared with model group (32.60±5.5vs.50.28±7.95; P＜0.001).3. Western Blot data showed us that the expression of P-Akt and p-S6K1showed no obvious difference in normal group and sham operation group (32.89±2.01vs.33.49±1.62;13.02±0.91vs.12.13±1.07). In model group, levels of P-Akt and p-S6K1were evidently increased (49.26±5.96vs.36.25±3.87) when compared with normal group or sham operation group. In intervention group, the expression of P-Akt and p-S6K1were significantly higher (76.99±2.07vs.61.49±5.67) than those in model group (P＜0.001).Conclusion:1. The expression of P-Akt and p-S6K1up-regulation after cerebral ischemia/reperfusion, the PI3K/Akt/mTOR/S6K1signal pathway may be one of endogenous mechanisms of autoprotection following cerebral ischemia/reperfusion injury of SD rats.2. Atorvastatin can promote the expression of P-Akt and p-S6K1after stress reaction of cerebral ischemia/reperfusion, the PI3K/Akt/mTOR/S6K1signal pathway may be one of the mechanisms to protect brain tissue from cerebral ischemia/reperfusion injury.