Effect of celastrol postconditioning on NF-κB，TNF-α，IL-1β in brain after focal cerebral ischemia-reperfusion injury in rats

Abstract:

Objective：To investigate the effects and the mechanism of celastrol postconditioning against focal cerebral ischemia-reper－fusion（I/R） injury in rats. Methods：Sixty-four SD rats with half males and half females were randomly divided into 4 groups（n=16）：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 models were produced by occlusion of middle cerebral artery for 2 h followed by 24 h of reper－fusion. Dimethyl sulfoxide（DMSO） 0.3 ml/kg was injected intraperitoneally after the sham operation in group S；celastrol 3 mg/kg was injected intraperitoneally after the sham operation in group S+C；DMSO 0.3 ml/kg was injected intraperitoneally at 5 min after the reperfusion in group I/R and celastrol 3 mg/kg was injected intraperitoneally at 5 min after the reperfusion in group I/R+C. The neu－rologic deficit scores were measured at 5 min before the reperfusion and at 24 h after the reperfusion. The infarct volume and the in－farct volume fraction were detected by TTC staining. The pathological changes in CA1 region of ischemic hippocampus were detected by HE staining. The content of tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in ischemic brain were detected by ELISA. The protein expression of nuclear factor-κB（NF-κB） p65 and inhibitor of κB（IκB）α in ischemic brain were detect－ed by Western blot. Results：The neurologic deficit scores，the infarct volume and the infarct volume fraction，the content of TNF-α and IL-1β，the protein expression of NF-κB p65 were all significantly higher in group I/R and I/R+C than in group S and S+C respectively. The protein expression of IκBα was significantly lower in group I/R and I/R+C than in group S and S+C respectively（P<0.01）. The neurologic deficit scores，the infarct volume and the infarct volume fraction，the content of TNF-α and IL-1β，the protein expression of NF-κB p65 were all significantly lower in group I/R+C than in group I/R and the protein expression of IκBα was significantly higher in group I/R+C than in group I/R（P<0.01）. The pathological changes in CA1 region of ischemic hippocampus were significantly attenuated in group I/R+C than in group I/R. The dif－ference between group S and group S+C was not statistical significant（P >0.05）. Conclusion：Postconditioning with celastrol attenuates focal cerebral I/R injury in rats；which might be related to inhibit the activaty of NF-κB，reduce the production of TNF-α and IL-1β，attenuate the inflammatory response in brain.