Objective To evaluate the role of autophagy in hippocampal neurons in cognitive dysfunction caused by sevoflurane anesthesia in juvenile rats.Methods One hundred four male SpragueDawley rats, aged 7 days, weighing 10-16 g, were randomly assigned into 3 groups using a random number table: control group (group C, n =8), sevoflurane anesthesia group (group S, n =48), and sevoflurane anesthesia + rapamycin group (group SR, n =48).Group C inhaled 60％ oxygen for 6 h.S and SR groups inhaled 3.6％ sevoflurane anesthesia for 6 h, and in addition, rapamycin 2 mg/kg was injected intraperitoneally at 1 h before of sevoflurane inhalation in group SR.The equal volume of phosphate buffer solution was given in C and S groups.At 1 h before sevoflurane anesthesia (T0) , immediately after the end of anesthesia (T1) , and at 12, 24 and 48 h after the end of anesthesia (T2-4) , 8 rats were randomly selected from S and SR groups to determine the expression of autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3) Ⅰ , LC3 Ⅱ and Beclin-1 in hippocampal neurons (by Western blot).The ratio of LC3 Ⅱ/LC3 Ⅰ was calculated.Morris water maze test was performed at 5 weeks after the end of anesthesia to assess the cognitive function.The escape latency, frequency of crossing the original platform, and duration of swimming spent at the target quadrant were recorded.Results Compared with the values at T0, the expression of LC3 Ⅱ and Beclin-1 was significantly down-regulated at T1-3 , and the ratio of LC3 Ⅱ/LC3 [was decreased in group S, and the expression of LC3 Ⅱ and Beclin-1 was significantly up-regulated at T1-4, and the ratio of LC3 Ⅱ/LC3 Ⅰ was increased in group SR (P＜0.05).Compared with group C, the escape latency was significantly prolonged, the frequency of crossing the original platform was reduced, and the duration of swimming spent at the target quadrant was shortened at 3-5 days in group S (P＜0.05) , and no significant change was found in the parameters mentioned above in group SR (P＞ 0.05).Compared with group S, the escape latency was significantly shortened, the frequency of crossing the original platform was increased, and the duration of swimming spent at the target quadrant was prolonged at 3-5 days, the expression of LC3 Ⅱ and Beclin-1 was up-regulated at T1-4 , and the ratio of LC3 Ⅱ/LC3Ⅰ was increased in group SR (P＜0.05).Conclusion Weakened autophagy in hippocampal neurons is involved in cognitive dysfunction caused by sevoflurane anesthesia in the juvenile rats.

Objective To evaluate the role of 2B-containing NMDA receptors(NR2B)in sevoflu-rane anesthesia-induced cognitive dysfunction in aged rats.Methods Thirty-two healthy male Sprague-Dawley rats,aged 18 months,weighing 570-630 g,were divided into 4 groups(n＝8 each)using a ran-dom number table method: control group(group C),sevoflurane anesthesia group(group S),sevoflurane anesthesia plus NR2B specific inhibitor Ro 25-6981 group(group S+RO)and Ro 25-6981 group(group RO).S and S+RO groups inhaled 3％sevoflurane for 4 h.Ro 25-6981 1 mg/kg was intraperitoneally injec-ted at 15 min before inhaling sevoflurane in group S+RO.Morris water maze test was performed at 2 days af-ter the end of anesthesia to assess cognitive function.The rats were then sacrificed,and hippocampal tis-sues were obtained for determination of the expression and phosphorylation of ERK1/2 by Western blot.Results Compared with group C,the escape latency was significantly prolonged,the frequency of crossing the original platform was reduced,the time of staying at the original platform quadrant was shortened,and the phosphorylation of ERK1/2 was decreased in group S(P＜0.05),and no significant change was found in the escape latency in S+RO and RO groups(P>0.05).Compared with group S,the escape latency was significantly shortened,the frequency of crossing the original platform was increased,the time of staying at the original platform quadrant was prolonged,and the phosphorylation of ERK1/2 was increased in group S+RO(P＜0.05).There was no significant difference in ERK1/2 expression among the four groups(P>0.05).Conclusion The mechanism by which sevoflurane anesthesia induces cognitive dysfunction is re-lated to up-regulating the expression of NR2B and inhibiting the activity of ERK1/2 in aged rats.

Objective: To evaluate the role of 2B-containing NMDA receptors (NR2B) in sevoflurane anesthesia-induced cognitive dysfunction in aged rats. Methods: Thirty-two healthy male Sprague-Dawley rats, aged 18 months, weighing 570-630 g, were divided into 4 groups (n=8 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group S), sevoflurane anesthesia plus NR2B specific inhibitor Ro 25-6981 group (group S+ RO) and Ro 25-6981 group (group RO). S and S+ RO groups inhaled 3% sevoflurane for 4 h. Ro 25-6981 1 mg/kg was intraperitoneally injected at 15 min before inhaling sevoflurane in group S+ RO.Morris water maze test was performed at 2 days after the end of anesthesia to assess cognitive function.The rats were then sacrificed, and hippocampal tissues were obtained for determination of the expression and phosphorylation of ERK1/2 by Western blot. Results: Compared with group C, the escape latency was significantly prolonged, the frequency of crossing the original platform was reduced, the time of staying at the original platform quadrant was shortened, and the phosphorylation of ERK1/2 was decreased in group S (P<0.05), and no significant change was found in the escape latency in S+ RO and RO groups (P>0.05). Compared with group S, the escape latency was significantly shortened, the frequency of crossing the original platform was increased, the time of staying at the original platform quadrant was prolonged, and the phosphorylation of ERK1/2 was increased in group S+ RO(P<0.05). There was no significant difference in ERK1/2 expression among the four groups (P>0.05). Conclusion The mechanism by which sevoflurane anesthesia induces cognitive dysfunction is related to up-regulating the expression of NR2B and inhibiting the activity of ERK1/2 in aged rats.