Effects of dexmedetomidine on activity of c-Jun N-terminal kinase during cerebral ischemia-reperfusion in rats

Objective To evaluate the effects of dexmedetomidine on the activity of c-Jun N-terminal kinase(JNK)during cerebral ischemia-reperfusion(I/R)in rats. Methods Eighty-one pathogen-free male Sprague-Dawley rats, aged 8 weeks, weighing 180-220 g, were randomly divided into 3 groups(n=27 each)using a random number table: sham operation group(group S); cerebral I/R group(group CI/R); dexmedetomidine group(group Dex). The rats were anesthetized with intraperitoneal 10% chloral hydrate 300 mg/kg.Cerebral ischemia was induced by occlusion of the middle cerebral artery for 2 h followed by 24 h of reperfusion in CI/R and Dex groups.The middle cerebral artery was only exposed but not occluded in group S. Dexmedetomidine 3 μg/kg was injected via the tail vein immediately before ischemia followed by infusion at a rate of 3 μg·kg-1·h-1until 24 h of reperfusion in group Dex, while the equal volume of normal saline was given in S and CI/R groups.The rats were sacrificed at 24 h of reperfusion, and their brains were removed for determination of cerebral infarct size(by TTC staining), brain water content((wet weight-dry weight)/wet weight × 100%), cell apoptosis(by TUNEL)and expression of phosphorylated JNK(p-JNK)protein(by Western blot analysis). Apoptotic index was calculated. Results Compared with group S, the brain water content, apoptotic index and cerebral infarct size were significantly increased, and the expression of p-JNK was up-regulated in CI/R and Dex groups.Compared with group CI/R, the brain water content, apoptotic index and cerebral infarct size were significantly decreased, and the expression of p-JNK was down-regulated in group Dex. Conclusion Dexmedetomidine reduces cerebral I/R injury through decreasing the activity of JNK and inhibiting cell apoptosis in rats. Key words: Dexmedetomidine; Reperfusion injury; Brain; JNK mitogen-activated protein kinases