Dexmedetomidine on autophagy of hippocampal neurons in aged rats under sevoflurane anesthesia

摘要

Dexmedetomidine is a highly-selective α adrenergic receptor agonist, widely used as an anesthesia adjuvant drug in clinic. Effects of dexmedetomidine on autophagy of hippocampal neurons and cognitive dysfunction in aged rats under sevoflurane anesthesia were investigated. Sixty healthy Sprague-Dawley (SD) rats aged 4–6 months of either sex, weighing 150–200 g were selected and randomly divided into control group (n=10), sevoflurane group (n=25) and dexmedetomidine + sevoflurane group (compound group, n=25). The control group was inhaled with 60% O2 for 6 h, the sevoflurane group was inhaled with 3.4–3.6% sevoflurane for 6 h, and the compound group was treated with intraperitoneal injection of 4 µg/kg dexmedetomidine 1 h before the inhalation of sevoflurane. Five rats were taken from each group 1 h before sevoflurane anesthesia (T1), immediately after anesthesia (T2), 12 h after anesthesia (T3) and 24 h after anesthesia (T4), respectively. The expression levels of microtubule-associated protein 1 light-chain 3-I (LC3-I), LC3-II and Beclin-1 were detected via western blotting, and the LC3-II/LC3-I value was calculated. Moreover, Morris water maze test was performed for the five rats in each group 5 weeks after anesthesia to detect the cognitive function; the escape latency, times across platform and swimming time in target quadrant were recorded. The levels of LC3-I, LC3-II and Beclin-1 in hippocampal neurons and LC3-II/LC3-I value in sevoflurane group at T2 were significantly higher than those at T1, and they reached the peak at T3, but were decreased at T4 (P<0.05); the levels of proteins and LC3-II/LC3-I value in compound group at T2 were significantly higher than those at T1 and reached the peak, and remained unchanged at T3-T4; besides, the level of proteins and LC3-II/LC3-I values in compound group at T2-T4 were obviously lower than those in sevoflurane group (P<0.05). In sevoflurane group, the escape latency was prolonged, the times across platform were reduced and the swimming time in target quadrant was shortened compared with those in control group (P<0.05); these parameters were significantly improved in compound group compared with those in sevoflurane group and control group (P<0.05). In conclusion, dexmedetomidine can improve the cognitive dysfunction in aged rats under sevoflurane anesthesia, which is related to the decreased autophagy of hippocampal neurons.