地佐辛联合异丙酚麻醉对大鼠海马组织p38MAPK信号通路及认知功能的影响

Effects of dizosin combined with propofol on p38MAPK signal pathway and cognitive function in hippocampus of rats

目的:探讨地佐辛联合异丙酚麻醉对大鼠海马组织p38MAPK及认知功能的影响。方法:选择30只SD大鼠,分为ZC组(正常大鼠)、YM组(异丙酚100 mg/kg麻醉大鼠)、DX组(地佐辛3 mg/kg+异丙酚100 mg/kg麻醉大鼠),进行水迷宫实验观察各组大鼠平均潜伏期、空间探索能力,HE染色观察海马组织结构,RT-PCR检测p38MAPK表达水平,Western blot法测定海马组织p38MAPK蛋白变化。结果:水迷宫实验发现,训练次数增多,大鼠的平均潜伏期出现显著降低,选择大鼠后4次逃避潜伏期进行计算,发现与ZC组对比,YM组大鼠平均潜伏期明显增长,DX组平均潜伏期低于YM组,高于ZC组(均P<0.05)。与ZC组大鼠对比,YM组大鼠在平台象限停滞时长变短,空间探索能力呈减弱趋势,DX组平台象限停留时间较YM组有所增加,但低于ZC组,空间探索能力较YM组有所增强(均P<0.05)。ZC组海马组织神经细胞排列紧密,细胞核完整。YM组海马组织神经细胞大量凋亡,排列紊乱且疏松,细胞核偏移。DX组海马组织神经细胞少量凋亡,细胞排列较稀疏,细胞核偏移较少。与ZC组对比,YM组p38MAPK水平明显增强,与YM组对比,DX组p38MAPK表达水平低于YM组,但高于ZC组(均P<0.05)。与ZC组对比,YM组p38MAPK蛋白表达显著增强,与YM组对比,DX组p38MAPK蛋白表达低于YM组,但高于ZC组(均P<0.05)。结论:异丙酚麻醉可激活p38MAPK活性,引起认知功能障碍,地佐辛联合异丙酚可抑制p38MAPK活性,对认知功能影响较小。

Objective:To investigate the effects of dizosin combined with propofol on p38MAPK signal pathway and cognitive function in hippocampus of anesthetized rats.Methods:Thirty SD rats were divided into ZC group(normal rats),YM group(rats anesthetized with 100 mg/kg propofol),DX group(rats anesthetized with 3 mg/kg Dizosin and 100 mg/kg propofol).The average latency and spatial exploration ability of rats in ZC group,YM group and DX group were observed by water maze test.Histological structure of hippocampus was observed by HE staining.The expression level of p38MAPK was detected by RT-PCR.The change of p38MAPK protein in hippocampus was detected by Western blot.Results:Water maze test found that the average latency of rats in each group decreased with the increase of training times.The average latency of rats in YM group was significantly longer than that in ZC group,and the average latency of rats in DX group was lower than that in YM group,higher than that in ZC group(all P<0.05).Compared with ZC group,YM group had shorter platform quadrant residence time and weaker space exploration ability,while DX group had more platform quadrant residence time than YM group,but lower than ZC group,and more space exploration ability than YM group(all P<0.05).In ZC group,the hippocampal neurons were arranged closely and the nucleus was intact.In YM group,a large number of neurons in hippocampus were apoptotic,disordered and loosely arranged,and the nucleus was migrated.In DX group,a small number of neurons in hippocampus were apoptotic,the arrangement of neurons was sparse,and the nuclear deviation was less.Compared with ZC group,the level of p38MAPK in YM group was significantly increased(P<0.05).The expression of p38MAPK in DX group was lower than that in YM group,but higher than that in ZC group(all P<0.05).Compared with ZC group,the expression of p38MAPK protein in YM group was significantly increased(P<0.05).The expression of p38MAPK protein in DX group was lower than that in YM group,but higher than that in ZC group(all P<0.05).Conclusion:Propofol anesthesia can activate the activity of p38MAPK and cause cognitive impairment.Dizosin combined with propofol can inhibit the activity of p38MAPK,and have little effect on cognitive function.