胞二磷胆碱对异氟醚麻醉致幼龄大鼠认知功能障碍的影响

Effects of citicoline on cognitive dysfunction induced by isoflurane anesthesia in juvenile rats

目的探讨胞二磷胆碱对异氟醚麻醉致幼龄大鼠认知功能障碍的影响。方法雄性sD大鼠54只，7日龄，体重15～20g，采用随机数字表法分为3组（n：18）：对照组（c组）、异氟醚麻醉组（I组）和异氟醚麻醉＋胞二磷胆碱组（IC组）。C组吸人纯氧4h，氧气流量4L／min；I组和Ic组吸人异氟醚4h，开始时浓度为3．4％～3．6％，1h后降至2．1％～2．3％，2～4h时1．7％～1．8％；吸入氧气或异氟醚结束后，Ic组腹腔注射胞二磷胆碱500mg／kg（用生理盐水稀释至O．5m1），C组和I组腹腔注射生理盐水0．5ml，1次／d，连续7d。分别于出生后14、30和60d时，采用条件恐惧实验测试认知功能，计算条件关联实验和条件暗示实验中大鼠凝滞时间百分比。于出生后60d条件恐惧实验结束后，处死大鼠，取海马组织，电镜下观察海马CAl区神经元超微结构。结果条件关联实验中，与C组比较，I组各时点凝滞时间百分比降低，Ic组出生后14d时凝滞时间百分比降低（P〈0．05）；与I组比较，Ic组出生后30和60d时凝滞时间百分比升高（P〈0．05），神经元损伤减轻。条件暗示实验中，3组问出生后各时点凝滞时间百分比比较差异无统计学意义（P〉0．05）。结论胞二磷胆碱可改善异氟醚麻醉致幼龄大鼠认知功能障碍。

Objective To investigate the effects of citicoline on cognitive dysfunction induced by isoflurane anesthesia in juvenile rats. Methods Fifty-four male Sprague-Dawley rats, aged 7 days, weighing 15-20 g, were randomly divided into 3 groups （n = 18 each） using a random number table： control group （C group） , isoflurane group （I group） , and isoflurane plus citicoline group （IC group）. Group C inhaled 100% oxygen at 4 L/min for 4 h. I and IC groups inhaled isoflurane for 4 h, and the initial concentration of isoflurane was 3.4%-3.6%, the concentration was decreased to 2.1%- 2.3% 1 h later, and to 1.7%-1.8% during 2-4 h. After the end of oxygen or isoflurane exposure, 500 mg/kg citicoline was intraperitoneally injected （ in 0.5 ml of normal saline） in IC group, and normal saline was given in C and I groups once a day for 7 consecutive days. On days 14, 30 and 60 after birth, cognitive function was assessed by contextual fear conditioning test, and then the percentage of freezing time was calculated during the context and cue tests. After the end of contextual fear conditioning test on day 60 after birth, rats were sacrificed, and the hippocampal tissue was extracted to examine the ultrastructure of neurons in hippocampal CA1 area with electron microscope. Results In the context test, compared to group C, the percentage of freezing time was significantly decreased at each time point in group I, and the percentage of freezing time was decreased on day 14 after birth in group IC; compared to group I, the percentage of freezing time was significantly increased on days 30 and 60 after birth, and the damage to neurons was mitigated in IC group. In the cue test, there was no significant difference among the three groups in the percentage of freezing time at each time point after birth. Conclusion Citicoline can improve cognitive dysfunction induced by isoflurane anesthesia in juvenile rats.