Effect of esmolol on expression of phosphorylated extracellular signal-regulated kinase 1/2 during cerebral ischemia-reperfusion in rats / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of esmolol on the expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) during cerebral ischemia-reperfusion (I/R) in rats.Methods:Forty-eight clean-grade healthy adult male Sprague-Dawley rats, were allocated into 3 groups ( n=16 each) using a random number table method: sham operation group (Sham group), cerebral I/R group (I/R group) and esmolol group (E group). Cerebral I/R was induced by 3 cycles of 20-min occlusion of bilateral common carotid arteries followed by 10-min reperfusion in anesthetized rats.Esmolol 200 g·kg -1·min -1 was intravenously infused for 1 h starting from 30 min before ischemia, and the model was established after 30-min infusion in E group.The equal volume of normal saline was given at 30 min before ischemia in I/R group.Bilateral common carotid arteries were only isolated but not clamped, and the equal volume of normal saline was given after isolating bilateral common carotid arteries in Sham group.Learning and memory function was tested by Morris water maze test before ischemia and at 1, 3 and 7 days of reperfusion.Rats were sacrificed after Morris water maze test, and the hippocampus was excised for determination of wet to dry weight ratio (W/D ratio), permeability of blood-brain barrier (using Evans blue method), expression of ERK1/2 mRNA (by real-time polymerase chain reaction ), and expression of p-ERK1/2 (by Western blot). Results:Compared with Sham group, the escape latency and swimming distance were significantly prolonged at 1, 3 and 7 days of reperfusion, the W/D ratio and EB content in brain tissues were increased, and the expression of ERK1/2 mRNA and p-ERK1/2 was up-regulated in I/R and E groups ( P<0.05). Compared with I/R group, the escape latency and swimming distance were significantly shortened at 1, 3 and 7 days of reperfusion, the W/D ratio and EB content in brain tissues were decreased, and the expression of ERK1/2 mRNA and p-ERK1/2 was down-regulated in E group ( P<0.05). Conclusion:The mechanism by which esmolol alleviates cerebral I/R injury and improves cognitive function is related to inhibiting the up-regulated expression of ERK1/2 in rats.