Effect of celastrol postconditioning on focal cerebral ischemia-reperfusion injury in rats

Abstract

Objective To evaluate the effect of celastrol postconditioning on focal cerebral ischemiareperfusion (I/R) injury in rats.Methods Sixty-four Sprague-Dawle rats (32 males,32 females),weighing 250300 g,were randomized into 4 groups using a random number table (n =16 each):sham operation group (group S) ; celastrol control group (group S + C) ; focal cerebral I/R group (group I/R) ; celastrol postconditioning group (group I/R + C).Focal cerebral I/R were produced by middle cerebral artery occlusion (MCAO).Dimethyl sulfoxide (DMSO) 0.3 ml/kg was injected intraperitoneally after shame operation in group S.Celastrol 3 mg/kg was injected intraperitoneally after shame operation in group S + C.DMSO 0.3 ml/kg was injected intraperitoneally at 5 min of reperfusion in group I/R.Celastrol 3 mg/kg was injected intraperitoneally at 5 min of reperfusion in group I/R + C.The neurologic deficit was scored at 5 min before reperfusion and 24 h of reperfusion.The infarct size was detected by TTC staining,and then the percentage of infarct size was calculated.The pathological changes in CA1 region of ischemic hippocampus were detected by HE staining.The activity of nicotinamide adenine dinucleotide phosphate oxidase (NOX),content of reactive oxygen species (ROS) and expression of NOX1 and NOX2 mRNA (by RT-PCR) in ischemic brain tissues were detected.Results Compared with S and S + C groups,the neurologic deficit scores,infarct size,percentage of infarct size,NOX activity and ROS content were significantly increased,and the expression of NOX1 mRNA and NOX2 mRNA was up-regulated in I/R and I/R + C groups (P ＜ 0.01).Compared with group I/R,the neurologic deficit scores,infarct size,percentage of infarct size,NOX activity and ROS content were significantly decreased,and the expression of NOX1 mRNA and NOX2 mRNA was down-regulated in group I/R+ C (P ＜ 0.01).There was no significant difference in the parameters mentioned above between group S and group S + C (P ＞ 0.05).The pathological changes in CAl region of ischemic hippocampus were significantly attenuated in group I/R + C (P ＜ 0.01).Conclusion Postconditioning with celastrol can auenuate focal cerebral [/R injury in rats and inhibiton of oxidative stress response in brain tissues may be involved in the mechanism. Key words: Tripterygium; Brain; Reperfusion injury; NADPH oxidase; Reactive oxygen species; Ischemic postconditioning