p38 MAPK antisense oligodeoxynucleotide inhibited up-regulation ofGLT-1 during induction of brain ischemic tolerance induced bycerebral ischemic preconditioning / 中国药理学通报

ABSTRACT

Aim To investigate the effect of p38 MAPK AS-ODNs on the expression of GLT-1 during the induction of brain ischemic tolerance induced by cerebral ischemic preconditioning (CIP).Methods Eighty healthy male Wistar rats with permanent occlusion of the bilateral vertebral arteries were randomly divided into 6 groups ①Sham group (n=10);②CIP group (n=10);③ischemic insult (Ⅱ) group (n=10);④CIP+Ⅱ group (n=10);⑤p38 MAPK AS-ODNs+CIP+Ⅱ group (n=30);⑥p38 MAPK S-ODNs+CIP+Ⅱ group (n=10).Group ⑤ was divided into 5 nmol, 10 nmol and 15 nmol subgroups according to the dose of p38 MAPK AS-ODNs (n=10).The dose of p38 MAPK S-ODNs was 15 nmol.All the rats were sacrificed 6 h and 2 d after the sham operation or the last time of global brain ischemia reperfusion.Western blot and immunohistochemistry analysis were used for detecting the expression of p-p38 MAPK and GLT-1 protein.Results CIP moderately up-regulated the expression of p-p38 MAPK and significantly up-regulated the expression of GLT-1 protein, inhibited the excessively up-regulation of p-p38 MAPK and the down-regulation of GLT-1 induced by ischemic insult.p38 MAPK AS-ODNs significantly inhibited the up-regulation of p-p38 MAPK and GLT-1 protein in a dose-dependent manner during the induction of brain ischemic tolerance by CIP.Conclusion p38 MAPK AS-ODNs inhibit the up-regulation of GLT-1 during the induction of brain ischemic tolerance induced by CIP.