Effect of isoflurane preconditioning on autophagy during focal cerebral ischemia-reperfusion injury in rats

Abstract

Objective To evaluate the effect of isoflurane preconditioning on autophagy during focal cerebral ischemia-reperfusion(I/R)injury in rats. Methods Thirty-six healthy male Sprague-Dawley rats, weighing 250-280 g, aged 7-8 weeks, were divided into 3 groups(n=12 each)using a random number table: sham operation group(group S), cerebral I/R group(group I/R)and isoflurane preconditioning group(group IP). Focal cerebral I/R was induced by 2 h middle cerebral artery occlusion followed by 24 reperfusion.Group IP inhaled 1.5% isoflurane for 1 h per day for 5 consecutive days, the other two groups only inhaled 30% oxygen, and focal cerebral I/R was induced at 24 h after the last inhalation.At 24 h of reperfusion, neurologic deficit was assessed and scored, the rats were then sacrificed, and brains were removed for determination of cerebral infarct size(using triphenyl tetrazolium chloride staining)and expression of microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)and Beclin-1(by Western blot). Results Compared with group S, the neurologic deficit scores and cerebral infarct size were significantly increased, and the expression of hippocampal LC3-Ⅱ and Beclin-1 was significantly up-regulated in I/R and IP groups(P<0.05). Compared with group I/R, the neurologic deficit scores and cerebral infarct size were significantly decreased, and the expression of hippocampal LC3-Ⅱ and Beclin-1 was significantly up-regulated in group IP(P<0.05). Conclusion The mechanism by which isoflurane preconditioning ameliorates focal cerebral I/R injury is related to enhancement of autophagy in the rats. Key words: Isoflurane; Ischemic preconditioning; Brain; Reperfusion injury; Autophagy