雷公藤红素下调p-p38、p-JNK、NF-κB减轻脑梗死后的炎症反应

Celastrol reduces inflammation after cerebral infarction by down-regulating p-p38,p-JNK and NF-κB

目的探讨脑缺血后磷酸化p38丝裂原活化蛋白激酶(p-p38)、磷酸化c-Jun氨基末端激酶(p-JNK)、核因子-κB(NF-κB)的表达变化,观察雷公藤红素的脑保护作用及机制。方法用改良线栓法制备大鼠大脑中动脉永久性脑梗死(pMCAO)模型。实验分为3组:溶剂对照组,假手术组和雷公藤红素组(3mg·kg^(-1)腹腔注射)。采用RT-qPCR和Western blot观察p-p38、p-JNK、NF-κB基因和蛋白表达变化,比较各组的患侧脑水肿、脑梗死体积和神经功能评分。结果与溶剂对照组相比,雷公藤红素组脑水肿明显低于溶剂对照组(P<0.05);梗死体积明显小于溶剂对照组(P<0.05);神经功能评分明显小于溶剂对照组(P<0.05);p-p38、p-JNK、NF-κB的表达明显低于溶剂对照组(P<0.05)。结论雷公藤红素对脑梗死大鼠具有脑保护作用,雷公藤红素通过调节p-p38,p-JNK和NF-κB的表达可能是其脑保护作用机制之一。

Objective To research the changes of p-p38,p-JNK and NF-κB after ischemic stroke and to study the underling mechanisms of celastrol.Methods Permanent middle cerebral occlusion(MCAO)was made in male Sprague-Dawley rats adopting modified suture occlusion technique.Rats were randomly classified into 3 groups:Celastrol group,sham group and vehicle group.The brain edema,neurological deficits,infarct volume,the expression of p-p38,p-JNK and NF-κB were measured at 24 h after cerebral ischemia.Results Celastrol group dramatically suppressed edema compared with vehicle rats.Celastrol group reduced neurological deficit compared with vehicle rats.Celastrol group showed smaller infarct volume compared with vehicle rats.Meanwhile,Celastrol group decreased the expression of p-p38,p-JNK and NF-κB compared with vehicle rats.Conclusion Celastrol protects the brain against pMCAO damage.The p-p38,p-JNK and NF-κB were involved in the protective effect of celastrol.