Relationship between autophagy and apoptosis during postoperative cognitive dysfunction in aged rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the relationship between autophagy and apoptosis during postoperative cognitive dysfunction in aged rats.Methods One hundred and twenty healthy male Sprague-Dawley rats,aged 18 months,weighing 500-550 g,were divided into 4 groups (n =30 each) using a random number tablecontrol group (group C),surgery group (group S),autophagy inhibitor 3-methyladenine group (group MA) and autophagy agonist rapamycin group (group R).Autophagy inhibitor 3-methvlade-nine 1 mg/kg and autophagy agonist rapamycin 2 mg/kg were injected via the caudal vein in MA and R groups,respectively,while the equal volume of normal saline was given instead in group S.Exploratory laparotomy was performed under anesthesia with 3％ sevoflurane 30 min later in S,MA and R groups.Ten rats of each group were selected on 1 day before operation and 3 and 7 days after operation,and Morris water maze test was performed to assess cognitive function.Then the rats were sacrificed,brains were removed and hippocampal tissues were obtained for detection of apoptosis in hippocampal neurons and the expression of microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ) and Beclin-1 by Western blot.The apoptotic rate was calculated.Results Compared with group C,the escape latency was significantly prolonged,the frequency of crossing the original platform was decreased,the apoptotic rate was increased,and the expression of LC3Ⅱ and Beclin-1 was down-regulated on 3 and 7 days after operation in S,MA and R groups (P＜0.05).Compared with group S,the escape latency was significantly prolonged,the frequency of crossing the original platform was decreased,the apoptotic rate was increased,and the expression of LC3 Ⅱ and Beclin-1 was down-regulated in group MA,and the escape latency was significantly shortened,the frequency of crossing the original platform was increased,the apoptotic rate was decreased,and the expression of LC3Ⅱ and Beclin-1 was up-regulated in group R (P＜0.05).Conclusion The mechanism of postoperative cognitive dysfunction is related to inhibiting autophagy and promoting apoptosis in hippocampal neurons of aged rats.