Effect of dexmedetomidine on expression of iNOS and COX-2 during focal cerebral ischemia-reperfusion in rats

Abstract

Objective To evaluate the effect of dexmedetomidine on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) during focal cerebral ischemia-reperfusion (I/R) in rats. Methods Thirty pathogen-free male Sprague-Dawley rats, aged 12-16 months, weighing 300-360 g, were randomly divided into 3 groups (n =10 each) using a random number table: sham operation group (group Sham), focal cerebral I/R group (group I/R), and dexmedetomidine group (group D). Focal cerebral I/R was induced by occlusion of the right middle cerebral artery.In group D, dexmedetomidine was given as a loading dose of 1 μg/kg (over 10 min) starting from 1 h of ischemia, followed by an infusion of 0.05 μg · kg-1 · h-1 until 2 h of reperfusion.Neurological deficit was assessed and scored at 24 h of reperfusion, and then the rats were sacrificed.Brains were removed for determination of cerebral infarct size and expression of iNOS and COX-2 in the hippocampus (by Western blot). The percentage of cerebral infarct size was calculated. Results Compared with group Sham, the neurological deficit score, percentage of head swing to the left, percentage of cerebral infarct size, and expression of iNOS and COX-2 in the hippocampus were significantly increased in I/R and D groups (P<0.05). Compared with group I/R, the neurological deficit score, percentage of head swing to the left, percentage of cerebral infarct size, and expression of iNOS and COX-2 in the hippocampus were significantly decreased in group D (P<0.05). Conclusion The mechanism by which dexmedetomidine mitigates focal cerebral I/R injury may be related to inhibition of iNOS and COX-2 expression in rats. Key words: Dexmedetomidine; Reperfusion injury; Brain; Nitric oxide synthase; Cyclooxygenase 2