Effects of NSC23766 on focal cerebral ischemia-reperfusion injury in diabetic rats

Abstract

Objective To investigate the effects of NSC23766 on focal cerebral ischemia-reperfusion (I/R) injury in diabetic rats.Methods Fifty-one male Sprague-Dawley rats,aged 2-3 months,weighing 250-300 g,in which diabetes mellitus was successfully induced by intraperitoneal streptozotocin 60 mg/kg,were randomly assigned into 3 groups (n=17 each): sham operation group (group S),focal cerebral I/R group (group I/R) and specific Racl inhibitor NSC23766 group (group N).Focal cerebral I/R was induced by middle cerebral arterial occlusion in groups I/R and N.In group N,NSC23766 (50 μg) was injected into the cerebral lateral ventricle at 15 min before ischemia,while the equal volume of normal saline was injected in groups S and I/R.Neurological deficits were scored at 24 h of reperfusion.The rats were then sacrificed and the brains were removed for determination of infarct volume (by TTC staining),apoptosis (by TUNEL) and phosphorylation of p38MAPK (by Western blot)and for microscopic examination (by HE and Nissl staining).Apoptotic index was calculated.Results Compared with group S,the neurological deficit scores aud apoptotic index were significantly increased,the infarct volume was enlarged,and the phosphorylation of p38MAPK was significantly increased in groups I/R and N (P ＜ 0.05).The neurological deficit scores and apoptotic index were significantly lower,and the infarct volume was significantly smaller,and the phosphorylation of p38MAPK was significantly lower in group N than in group I/R (P ＜ 0.05).Conclusion NSC23766 can reduce focal cerebral I/R injury in diabetic rats. Key words: racl GTP-binding protein; Diabetes mellitus; Reperfusion injury; Brain