摘要目的：探讨在异氟烷麻醉总时间一致的前提下，不同麻醉时间间隔对发育期大鼠急性脑损伤后认知行为的影响。方法选用生后7d的SD大鼠，按随机数字表法分为正常对照组（呼吸空气）、连续麻醉组（异氟烷持续给药6h）、间隔麻醉1d和3d组（异氟烷给药2h×3次，间隔1d或3d），每组12只，雌雄比为5：7。生后21d进行八臂迷宫行为测试，每日2次，连测4d。根据大鼠进入八臂迷宫的错误次数、重复错误次数、入臂总次数和总耗时，评价异氟烷麻醉对发育期大鼠认知行为的影响。结果①与正常对照组相比，间隔麻醉3d组错误次数＞3次的百分比明显减少（33.3%比46.9%，P＜0.05），重复错误次数＞0次的百分比和入臂总次数＞8次的百分比明显增多（33.3%比18.8%，27.1%比13.5%，均P＜0.05）；连续麻醉组、间隔麻醉1d组错误次数＞3次的百分比与正常对照组比较差异无统计学意义（44.8%、44.8%比46.9%），重复错误次数＞0次和入臂总次数＞8次的百分比均较正常对照组略有增加（27.1%、22.9%比18.8%，20.8%、21.9%比13.5%，均P＞0.05）。正常对照组、连续麻醉组、间隔麻醉1d和3d组入臂总耗时差异均无统计学意义（min：1.32±0.91、1.54±1.05、1.46±0.86、1.38±0.79，均P＞0.05）。②性别分析发现，仅正常对照组雌鼠重复错误次数＞0次的百分比及入臂总次数＞8次的百分比明显低于雄鼠（5.0%比28.6%，P＜0.01；5.0%比19.6%，P＜0.05），其余各组内雌、雄鼠之间各指标均无明显差异。③组间比较显示，连续麻醉组、间隔麻醉1d和3d组雌鼠重复错误次数＞0次的百分比均较正常对照组雌鼠明显增高（25.0%、25.0%、30.0%比5.0%，P＜0.05或P＜0.01），间隔麻醉1d和3d组雌鼠入臂总次数＞8次的百分比均较正常对照组雌鼠明显增高（22.5%、25.0%比5.0%，均P＜0.05）；而各处理组雄鼠在八臂迷宫认知测试中与正常对照组雄鼠相比差异均无统计学意义。结论异氟烷不同间隔时间给药麻醉可以造成发育期大鼠一定程度的急性脑损伤，表现为认知障碍，延长麻醉间隔时间可明显增强长期记忆能力，多次麻醉处理比单次对认知的影响更大，雌性较雄性更易发生麻醉后认知功能的改变。

abstractsObjective To investigate effects of isoflurane anesthesia of different time interval on acute injury of brain function in neonatal rats with consistent total time of isoflurane anesthesia. Methods Seven-day neonatal Sprague-Dawley (SD) rats were randomly divided into normal control group (breathe the air), continuous anesthesia group (a single 6-hour exposure to 1.5% isoflurane), and intermittent anesthesia 1 day and 3 days groups (three times of 2-hour exposure to anesthesia with an interval of 1 day or 3 days), 12 rats in each group. The ratio of male to female was 5:7. They underwent the test of learning and memory in the radial arm maze (RAM) 21 days after birth, twice a day for 4 days. The number of entry into wrong arms, number of repeated errors, number of total arm entries, and time for completing the task were recorded for evaluation of effect of neonatal isoflurane on cognitive behavior in rats. Results ① Compared with normal control group, the percentage of number of errors > 3 in anesthesia of 3-day interval group was significantly decreased (33.3% vs. 46.9%, P < 0.05), the percentages of repeated errors > 0 and total arm entries > 8 were significantly increased (33.3% vs. 18.8%, 27.1% vs. 13.5%, both P < 0.05), but there were no statistically significant difference in the percentage of mistake number > 3 between continuous anesthesia group, interval anesthesia 1-day group and the normal control group (44.8%, 44.8% vs. 46.9%), the percentages of number of repeated mistake > 0 and total arm entries > 8 in above three groups were slightly increased as compared with those of normal control group (27.1%, 22.9% vs. 18.8%, 20.8%, 21.9% vs. 13.5%, all P > 0.05). No statistical differences in completing the task among normal control group, continuous anesthesia group, interval anesthesia 1 day and 3 days groups were found (minutes: 1.32±0.91, 1.54±1.05, 1.46±0.86, 1.38±0.79, all P > 0.05). ② It was found by gender analysis that the percentages number of repeated errors > 0 and total arm entries > 8 were significantly lower in female rats than those in the male rats only in normal control group (5.0% vs. 28.6%, P < 0.01; 5.0% vs. 19.6%, P < 0.05). There was no obvious gender difference in exposed groups. ③ Compared between groups of female rats, the percentages of repeated mistake > 0 in continuous anesthesia group, interval anesthesia 1 day and 3 days groups (25.0%, 25.0%, 30.0% vs. 5.0%, P < 0.05 or P < 0.01) and the percentage of total arm entries > 8 in interval anesthesia 1 day and 3 days groups were significantly higher than that of normal control group (22.5%, 25.0% vs. 5.0%, both P < 0.05). No significant difference about the RAM task in male rats of all the four groups was found. Conclusions Different time interval of neonatal isoflurane exposure may develop certain degree of acute brain injury in rats, characterized by cognitive function. Prolongation of the interval time significantly enhanced long-term memory in rats. Multiple neonatal exposures to isoflurane were associated with greater cognitive impairment than a single exposure. In addition, isoflurane can significantly increase cognitional functional disorder in the female, not in the male rats.