反复吸入七氟醚对大鼠海马神经元p-cofilin及cofilin表达和远期认知功能的影响

Effects of repeated inhalation of sevoflurane on expression of p-cofilin,cofilin in rat hippocampal neurons and long-term cognitive function

目的探讨反复吸入七氟醚对大鼠海马神经元磷酸化丝切蛋白(p-cofilin)及丝切蛋白(cofilin)表达和远期认知功能的影响。方法将20只雄性SD大鼠随机分为七氟醚组(n=10)和对照组(n=10),七氟醚组大鼠吸入2.4%七氟醚,每日2 h,连续7 d,对照组不吸入七氟醚。通过Morris水迷宫定位航行实验及空间探索实验检测两组大鼠认知功能,采用TUNEL实验检测海马神经元凋亡情况,Western Blot检测海马内Bax、Bcl-2、p-cofilin和cofilin表达情况。结果定位航行实验的第3、4、5d,七氟醚组逃避潜伏期长于对照组,差异有统计学意义(P<0.05);两组大鼠空间探索实验结果发现,七氟醚组大鼠穿越平台次数明显少于对照组,平台象限停留时间明显短于对照组(均P<0.05);两组游泳速度无明显差异(P>0.05);与对照组比较,七氟醚组大鼠海马组织凋亡细胞数目明显增加(P<0.05);七氟醚组Bax表达明显高于对照组,而Bcl-2表达明显低于对照组(P<0.05);七氟醚组p-cofilin表达明显低于对照组,而cofilin表达明显高于对照组(P<0.05)。结论反复吸入七氟醚可降低大鼠认知功能,其机制可能与上调cofilin表达诱导的细胞凋亡有关。

Objective To investigate the effects of repeated inhalation of sevoflurane on long-term cognitive function in rats and the expression of p-cofilin and cofilin in hippocampal neurons.Methods 20 male Sprague-Dawley rats were randomly divided into Sevoflurane group(n=10)and Control group(n=10).Sevoflurane rats inhaled 2.4%sevoflurane for 2 h for 7 d and Control group did not.The cognitive function of the two groups of rats was detected by Morris water maze navigation experiment and space exploration experiment.The apoptosis of hippocampal neurons was detected by TUNEL assay.The expression of cofilin,Bax,Bcl-2,and p-cofilin in hippocampus was detected by Western Blot.Results On the 3 rd,4 th and 5 th day of the navigation experiment,the escape latency of Sevoflurane group was longer than that of Control group(P<0.05).The results of space exploration experiments in the two groups showed that the number of rats crossing the platform of Sevoflurane group was significant less that of Control group.The plate quadrant dwell time of Sevoflurane group was significantly shorter than that of Control group(P<0.05).There was no significant difference in swimming speed between the two groups(P>0.05).The number of apoptotic cells in the hippocampus of Sevoflurane group was significantly higher than that in Control group.The expression of Bax and cofilin in the Sevoflurane group were significantly higher than that in the Control group(P<0.05),and the expression of Bcl-2 and p-cofilin were significantly lower than that in the Control group(P<0.05).Conclusion Repeated inhalation of sevoflurane may reduce cognitive function in rats,and its mechanism may be related to up-regulation of apoptosis induced by cofilin expression.