异氟醚后处理对缺血缺氧性脑损伤新生大鼠远期认知功能的影响

Effects of isoflurane postconditioning on long-term cognitive function of neonatal rats with hypoxic-ischemic brain injury

目的 评价异氟醚后处理对缺血缺氧性脑损伤新生大鼠远期认知功能的影响.方法 新生SD大鼠60只,雌雄不拘,7d龄,体重12 ～ 16 g,采用随机数字表法分为4组（n=15）：假手术组（S组）、异氟醚后处理组（IS组）、脑缺血缺氧组（HIBI组）和脑缺血缺氧＋异氟醚后处理组（HIBI＋ IS组）.HIBI组和HIBI＋ IS组永久性结扎左侧颈总动脉后,置于低氧环境（8％ O2-92％N2混合气体）2h,以制备缺血缺氧性脑损伤模型.S组和IS组分离左侧颈总动脉（只穿线不结扎）,不制备模型.于低氧2h后,IS组和HIBI＋ IS组持续吸入1.5％异氟醚（30％O2-70％N2混合气体）30 min;S组和HIBI组吸入30％O2-70％N2混合气体30 min.于第30-35天行Morris水迷宫实验,记录逃逸潜伏期、搜索速度、搜索路程、穿平台次数、平台象限时间百分比及平台象限路程百分比等;于水迷宫实验结束处死大鼠取脑,计算丘脑腹后内侧核和海马CA3区左、右侧正常神经元密度比值.结果 与S组比较,HIBI组第30-34天逃逸潜伏期延长,HIBI＋ IS组第31和34天逃逸潜伏期延长,HIBI组第35天穿平台次数、平台象限时间百分比、平台象限路程百分比、丘脑腹后内侧核及海马CA3区左、右侧神经元密度的比值降低（P＜0.05）,HIBI＋ IS组第35天穿平台次数、平台象限时间百分比及平台象限路程百分比差异无统计学意义（P＞0.05）,丘脑腹后内侧核及海马CA3区左、右侧神经元密度的比值降低（P＜0.05）,IS组上述各项指标差异无统计学意义（P＞0.05）;与HIBI组比较,HIBI＋ IS组第31-34天逃逸潜伏期缩短,第35天穿平台次数、平台象限时间百分比、平台象限路程百分比、丘脑腹后内侧核及海马CA3区左、右侧神经元密度的比值升高（P＜0.05）;各组第35天搜索速度及搜索路程比较差异无统计学意义（P＞0.05）.结论 异氟醚后处理可改善缺血缺氧性脑损伤新生大鼠的远期认知功能.

Objective To evaluate the effects of isoflurane postconditioning on long-term cognitive function of neonatal rats with hypoxic-ischemic brain injury （HIBI）.Methods Sixty 7-day-old Sprague-Dawley rats,weighing 12-16 g,were randomly divided into 4 groups （n =15 each） using a random number table：sham operation group （group Ⅰ）,isoflurane postconditioning group （group Ⅱ）,cerebral hypoxia-ischemia group （group Ⅲ）,and isoflurane postconditioning after cerebral hypoxia-ischemia group （group Ⅳ）.Brain ischemia was induced by permanent ligation of the left common carotid artery followed by inhalation of 8 % O2-92 % N2 for 2 h at 37 ℃ in Ⅲ and Ⅳ groups.In Ⅰ and Ⅱ groups,the left common carotid artery was only isolated but not ligated.The rats inhaled 1.5% isoflurane in 30% O2-70% N2 for 30 min starting from 2 h of hypoxia in Ⅱ and Ⅳ groups.The rats were exposed to 30% O2-70% N2 for 30 min in Ⅰ and Ⅲ groups.Morris water maze test was carried out at 30-35 days after HIBI.The escape latency,swimming speed,swimming distance,the number of times the animals crossing the platform quadrant,the percentage of time spent in the platform quadrant and the percentage of swimming distance in the platform quadrant were recorded.The animals were sacrificed after Morris water maze test.The density of normal neurons in ventral posterior inferior thalamic nucleus and hippocampal CA3 region in left and right cerebral hemisphere was measured and the ratio of the density of normal neurons in the left to right cerebral hemisphere was calculated.Results Compared with group Ⅰ,the escape latency was significantly prolonged at 30-34 days after HIBI in group Ⅲ and at 31 and 34 days after HIBI in Ⅳ group,the number of times the animals crossing the platform quadrant,percentage of time spent in the platform quadrant,percentage of swimming distance in the platform quadrant,and ratio of the density of normal neurons in the left to right cerebral hemisphere were decreased at day 35 after HIBI in group Ⅲ,no significant changes were found in the number of times the animals crossing the platform quadrant,percentage of time spent in the platform quadrant,and percentage of swimming distance in the platform quadrant,and the ratio of the density of normal neurons in the left to right cerebral hemisphere was decreased at day 35 after HIBI in group Ⅳ,and no significant changes were found in the parameters mentioned above in group Ⅱ.Compared with group Ⅲ,the escape latency was significantly shortened at 31-34 days after HIBI,and the number of times the animals crossing the platform quadrant,percentage of time spent in the platform quadrant,percentage of swimming distance in the platform quadrant,and ratio of the density of normal neurons in the left to right cerebral hemisphere were increased at day 35 after HIBI in group Ⅳ.There was no significant difference in the swimming speed and swimming distance at day 35 after HIBI between groups.Conclusion Isoflurane postconditioning can improve long-term cognitive function of neonatal rats with HIBI.