Effect of melatonin on postoperative apoptosis in hippocampal cells of aged rats undergoing isoflurane anesthesia

Abstract

Objective To evaluate the effect of melatonin on postoperative apoptosis in hippocampal cells of aged rats undergoing surgery under isoflurane anesthesia. Methods Sixty healthy male Sprague-Dawley rats, aged 18 months, weighing 550–610 g, were randomized into 5 groups(n=12 each)using a random number table: control group(group C), 2% isoflurane anesthesia group(group I), 2% isoflurane + melatonin group(group IM), surgery group(group S), and surgery + melatonin group(group SM). Group IM inhaled 2% isoflurane for 4 h. Group S inhaled 2% isoflurane for 4 h, and then back surgery was performed.In IM and SM groups, melatonin 10 mg/kg was injected intraperitoneally everyday for 7 consecutive days before anesthesia, while the equal volume of normal saline was given in C, I and S groups.The cognitive function was assessed using the Morris water maze test on 2nd after anesthesia.The escape latency, space exploration time spent at the original platform quadrant, and frequency of crossing the original platform were recorded.After the end of the Morris water maze test, the rats were sacrificed on that day, and the hippocampi were isolated for detection of the expression of Bcl-2, Bax and caspase-3 by Western blot.Bcl-2/Bax ratio was calculated. Results Compared with group C, the escape latency was significantly prolonged on days 1-3 after anesthesia in group I, the escape latency was significantly prolonged, the space exploration time spent at the original platform quadrant was shortened, and the frequency of crossing the original platform was decreased on days 1-3 after operation in group S, and the expression of caspase-3 and Bax was significantly up-regulated, the expression of Bcl-2 was down-regulated, and Bcl-2/Bax ratio was decreased in I and S groups(P 0.05). Compared with group S, the escape latency was significantly shortened, the space exploration time spent at the original platform quadrant was prolonged, and the frequency of crossing the original platform was increased on days 3-5 after operation, the expression of caspase-3 and Bax was significantly down-regulated, the expression of Bcl-2 was up-regulated, and Bcl-2/Bax ratio was increased in group SM(P<0.05). Conclusion Melatonin can inhibit apoptosis in hippocampal cells and improve postoperative cognitive dysfunction in aged rats undergoing isoflurane anesthesia. Key words: Melatonin; Isoflurane; Anesthesia; Postoperative complications; Cognition disorders; Apoptosis; Hippocampus