Objective:To evaluate the effect of dexmedetomidine pretreatment on the autophagy of hippocampal neurons in the developing rats under sevoflurane anesthesia.Methods:Thirty-six clean-grade healthy Sprague-Dawley rats of either sex, aged 7 days, weighing 12-15 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), sevoflurane group (group S), and sevoflurane plus dexmedetomidine group (group S+ D). On 7-9 days after birth, and the animals were exposed to 3% sevoflurane (oxygen concentration inhaled 29%, oxygen flow 2 L/min, 2 h/day) after intraperitoneal injection of 25 μg/kg dexmedetomidine every day in group S+ D, the animals were exposed to sevoflurane after intraperitoneal injection of the equal volume of normal saline in group S, and the animals were exposed to gas mixture after intraperitoneal injection of the equal volume of normal saline in group C. The Morris water maze test was carried out at 20 days after birth, and the place navigation test and spatial probe test were performed.After the end of Morris water maze test, the anesthetized rats were sacrificed, and the hippocampus was obtained for determination of the expression of microtubule-associated protein light chain 3(LC3), BECN1 and P62 by Western blot. Results:Compared with group C, the escape latency was significantly prolonged, the frequency of crossing the original platform was decreased, the expression of LC3 and BECN1 was up-regulated, and the expression of P62 was down-regulated in group S and group S+ D ( P<0.05). Compared with group S, the escape latency was significantly shortened, the frequency of crossing the original platform was increased, the expression of LC3 and BECN1 was down-regulated, and the expression of P62 was up-regulated in group S+ D ( P<0.05). Conclusions:The mechanism by which dexmedetomidine pretreatment improves sevoflurane-induced cognitive dysfunction is related to reduction of excessive autophagy in hippocampal neurons of developing rats.