异氟醚对胎鼠脑原癌基因蛋白Bcl-2/Bax表达及幼鼠空间学习记忆的影响

目的 研究异氟醚麻醉对胎鼠出生后的学习记忆能力,以及对胎鼠大脑海马CA1区和皮质压部后区(Retrosplenial RS)Bcl-2/Bax表达变化的影响.方法 28只孕21 d的大鼠以随机数字表法随机分为异氟醚处理组和对照组,每组n=14.异氟醚组使用1.3%的异氟醚处理6h,对照组只使用30%的氧气和70%氮气混合气.使用水迷宫检测出生后28d的幼鼠空间学习记忆能力.免疫组化研究中,处理后2 h检测胎鼠大脑皮质RS区和海马CA1区Bcl-2和Bax表达的变化.结果 水迷宫实验中,2组隐藏平台试验的逃避潜伏期差异没有统计学意义,但是空间探索试验中异氟醚组在平台所在象限停留的时间明显多于对照组(42.33±2.31)s,(33.2±2.15)s,t=2.21,P<0.05],差异有统计学意义.异氟醚组海马CA1区和皮质RS区Bcl-2的表达高于对照组,Bax的表达低于对照组,Bcl-2/Bax比值高于对照组海马CA1区(4.40±0.86),(1.31±0.32),t=3.378,P<0.01;皮质RS区(5.07±1.27),(1.47±0.48),t=2.656,P<0.05],差异具有统计学意义.结论 1.3%异氟醚处理孕21 d的大鼠能改善出生后幼鼠的空间记忆保持能力,并能增加胎鼠大脑皮质RS区和海马CA1区Bcl-2/Bax的比值.

The effects of isoflurane on the ratio of Bcl-2/Bax in rat fetal brain and spatial learning ability at juvenile age

Objective To determine whether fetal rats exposure to isoflurane will cause postnatal learning and memory deficits,and change Bcl-2/Bax ratio in the hippocampus CA1 and retrosplenial cortex in fetal brain of rats. Methods Twenty-eight Sprague Dawley pregnant rats at gestation day 21 (E21) were randomly divided into isoflurane treatment group(n=14) and sham control group(n=14). Rats in isoflurane treatment group were ex-posed to 1.3% isoflurane in a carrying gas of 30% oxygen, balance nitrogen for 6 h in a warmed, humidified cham-ber. For sham control group,animals were treated at the same condition with only carrying gas. In behavior study,the spatial learning and memory ability at juvenile ages was determined with the Morris Water Maze(MWM). In immunohistochemistry study,changes of Bcl-2 and Bax expression in hippocampus CA1 and retrosplenial cortex in the fetus brain after isoflurane treatment at 2 hours was performed by using immunofluorecence staining.Results In the MWM training, the escape latency to platform in the place trials showed no significant difference between the two groups,but the postnatal rats in 1.3% isoflurane group showed obviously improved retention of memory by spending more percentage of time swimming in the probe quadrant as compared to the control animals ((42.33±2.31) s vs (33.2±2.15) s, t=2.21, P<0.05) in the probe test. Compared to controls, 1.3% isoflu-rane exposure for 6 h to the pregnant rats increased the intensity of Bcl-2, decreased the intensity of Bax, and sig-nificantly increased the Bcl-2/Bax ratio in the fetal hippocampal CA1 region (4.40±0. 86 vs 1.31±0.32, t=3. 378, P<0.01) and the fetal retrosplenial cortex (5.07±1.27 vs 1.47±0.48, t=2.656, P < 0.05) respec-tively. Conclusion 1.3% isoflurane exposure in pregnant rats significantly improves the spatial retention memo-ry of their rat pups at a juvenile age and increases the Bcl-2/Bax ratio in the hippocampal CA1 region and the ret-resplenial cortex in the fetal rat brains.