Guo Shanbin, Liu Lidan, Wang Cong, Jiang Qian, Dong Yunxia, Tian Yue
Department of Pharmacy, Shengjing Hospital of China Medical University, No 36, Sanhao Street, Herping District, Shenyang 110004, China.
Department of Anaesthesiology, Shengjing Hospital of China Medical University, No 36, Sanhao Street, Herping District, Shenyang 110004, China.
Life Sci. 2018 Jan 1;192:75-83. doi: 10.1016/j.lfs.2017.11.025. Epub 2017 Nov 17.
Critically ill old patients sometimes require repeated surgical interventions, and thus it is important to determine the influence of repeated exposure to anesthetics on learning and memory. Sevoflurane, a widely used inhalation anesthetic, has few neurological adverse effects and offers a rapid return to consciousness. But the long-term influence of sevoflurane exposure and the effect of repeated sevoflurane exposure on cognition have rarely been reported, and available studies are contradictory.
In the present study, the Morris water maze test was employed to investigate the long-term influence of single (4h) or repeated (2h daily for 5 consecutive days) exposure to 1.5% or 2.5% sevoflurane on the learning ability and memory of old (16-18months old) male rats. Testing was performed from 1day to 4weeks after the last exposure. In the hippocampus, brain derived neurotrophic factor (BDNF), NF-κB mRNA, and apoptosis rate were also examined to determine whether cellular biochemical changes related to cognition and memory occurred after single or repeated exposure to sevoflurane.
Repeated exposure to 2.5% sevoflurane decreased hippocampal levels of BDNF protein, enhanced hippocampal levels of NF-κB mRNA, and increased the apoptosis rate of pyramidal cells. Single exposure to 2.5% sevoflurane, and repeated exposure to either 1.5% or 2.5% sevoflurane significantly compromised learning and memory of old male rats.
Repeated exposure to sevoflurane impaired the learning and memory of old male rats, an impairment that was accompanied by cognition-related biochemical changes in the hippocampus.
重症老年患者有时需要反复进行外科手术干预，因此确定反复接触麻醉剂对学习和记忆的影响很重要。七氟烷是一种广泛使用的吸入性麻醉剂，几乎没有神经方面的不良反应，且能使患者迅速苏醒。但是，七氟烷暴露的长期影响以及反复暴露于七氟烷对认知的影响鲜有报道，现有研究结果也相互矛盾。
在本研究中，采用莫里斯水迷宫试验来研究单次（4小时）或反复（连续5天每天2小时）暴露于1.5%或2.5%七氟烷对老年（16 - 18月龄）雄性大鼠学习能力和记忆的长期影响。在最后一次暴露后的第1天至第4周进行测试。还检测了海马体中脑源性神经营养因子（BDNF）、NF-κB mRNA和凋亡率，以确定单次或反复暴露于七氟烷后是否发生了与认知和记忆相关的细胞生化变化。
反复暴露于2.5%七氟烷会降低海马体中BDNF蛋白水平，提高海马体中NF-κB mRNA水平，并增加锥体细胞的凋亡率。单次暴露于2.5%七氟烷以及反复暴露于1.5%或2.5%七氟烷均会显著损害老年雄性大鼠的学习和记忆能力。
反复暴露于七氟烷会损害老年雄性大鼠的学习和记忆能力，这种损害伴随着海马体中与认知相关的生化变化。
