Role of Akt∕GSK-3β signaling pathway in trichostatin-A-induced reduction of cerebral ischemia-reperfusion injury in mice / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of protein kinase B∕glycogen synthase kinase-3 beta (Akt∕GSK-3β) signaling pathway in trichostatin-A (TSA)-induced reduction of cerebral ischemia-reperfu-sion ( I∕R) injury in mice. Methods Forty pathogen-free healthy male Balb∕c mice, weighing 18-22 g, were divided into 4 groups ( n=10 each) using a random number table method: sham operation group ( S group), I∕R group, TSA group and TSA plus Akt inhibitor LY294002 group (TL group). Cerebral I∕R was induced by middle cerebral artery occlusion ( 1-h ischemia followed by 24-h reperfusion) . TSA 5 mg∕kg was intraperitoneally injected for 3 consecutive days before establishing the model in TSA group. TSA 5 mg∕kg was intraperitoneally injected for 3 consecutive days before establishing the model, and LY29400215 nmol∕kg was injected via the caudal vein at 30 min before establishing the model. Brain tissues were ob-tained at 24 h of reperfusion for determination of cerebral infarct size ( by TTC ) , activities of superoxidedismutase ( SOD) and reactive oxygen species ( ROS) and malondialdehyde ( MDA) content ( by colorimet-ric assay), cell apoptosis (by TUNEL) and expression of Akt, phosphorylated Akt (p-Akt), GSK-3βand phosphorylated GSK-3β ( p-GSK-3β) . The apoptosis index and ratios of p-Akt∕Akt and p-GSK-3β∕GSK-3β were calculated. Results Compared with S group, the cerebral infarct size was significantly in-creased, the activity of SOD in brain tissues was decreased, the MDA content and ROS activity in brain tissues and apoptosis index were increased, and the ratios of p-Akt∕Akt and p-GSK-3β∕GSK-3β were de-creased in I∕R group ( P<0. 05) . Compared with I∕R group, the cerebral infarct size was significantly de-creased, the activity of SOD in brain tissues was increased, the MDA content and ROS activity in brain tis-sues and apoptosis index were decreased, and the ratios of p-Akt∕Akt and p-GSK-3β∕GSK-3β were de-creased in TSA group ( P<0. 05) . Compared with TSA group, the cerebral infarct size was significantly in-creased, the activity of SOD in brain tissues was decreased, the MDA content and ROS activity in brain tissues and apoptosis index were increased, and the ratios of p-Akt∕Akt and p-GSK-3β∕GSK-3β were de-creased in TL group ( P<0. 05) . Conclusion The mechanism by which TSA attenuates cerebral I∕R injury is related to activating Akt∕GSK-3β signaling pathway in mice.