基质金属蛋白酶-9表达下调在异丙酚麻醉诱发大鼠学习记忆障碍中的作用

Role of matrix metalloproteinase-9 down-regulation in learning and memory dysfunction induced by propofol treatment in rats

目的探讨基质金属蛋白酶-9(MMP-9)表达下调在异丙酚麻醉诱发大鼠学习记忆障碍中的作用。方法 7 d龄SD大鼠随机分为3组(n=18):对照组(NS组)和多次异丙酚麻醉组(RP组)连续7 d分别腹腔注射生理盐水和异丙酚,单次异丙酚麻醉组(SP组)前6天连续腹腔注射生理盐水,d 7注射异丙酚。各组随机选取6只大鼠进行动脉血气和血糖监测,剩余大鼠行Morris水迷宫测试其学习记忆能力,Western bolt法检测MMP-9、BDNF、caspase-3的表达;TUNEL染色法测定海马神经元的凋亡。结果与NS组和SP组相比,RP组大鼠逃逸潜伏期明显延长,探索时间和穿越平台次数明显减少(P<0.05),海马MMP-9、m BDNF表达减弱,pro BDNF表达、pro BDNF/m BDNF比值增加(P<0.05),神经元凋亡细胞数量明显增多,pro-caspase-3表达减低,cleaved-caspase-3表达增高(P<0.05)。而SP组与NS组相比,各结果差异均无显著性(P>0.05)。结论多次注射异丙酚导致新生大鼠远期学习记忆能力下降,可能与海马MMP-9表达下调,pro BDNF、m BDNF成熟转换障碍以及海马神经元凋亡发生有关;而单次注射异丙酚对此影响不明显。

Aim To investigate the role of matrix metalloproteinase-9 down-regulation in the learning and memory dysfunction induced by propofol treatment in rats.Methods 7-day-old SD rats were randomlydivided into three groups（n = 18）：control group（NS group） and repeated doses of propofol group（RP group） was intraperitoneally injected with normal saline and propofol respectively for consecutive seven days,single dose of propofol group（SP group） were intraperitoneally injected with normal saline first for consecutive six days,and then injected with propofol on 7th day.The blood gas and glucose levels were monitored of six rats randomly selected from each group.Morris water maze was conducted to test the learning and memory functions of the remaining rats.The expression of MMP-9,BDNF and caspase-3 was detected by Western blot,and the hippocampal neuron apoptosis was determinated by TUNEL staining.Results Compared with NS group and SP group,the escape latency in RP group was prolonged significantly,exploration time and the number of crossing the platform in RP group were markedly decreased（P〈0.05）.The expressions of MMP-9 and mB DNF in RP group de-clined,but the expression of pro BDNF and the ratio of pro BDNF/mB DNF in RP group were higher than those in NS group and SP group（P〈0.05）.Compared with NS group and SP group,the number of apoptotic neurons and the expression of cleaved-caspase-3 in RP group were increased significantly,but the expression of pro-Caspase3 in RP group was reduced（P〈0.05）.There was no difference between SP group and NS group regarding all the results（P〈0.05）.Conclusions Repeated exposure to propofol can lead to a decline in long-term learning and memory functions in neonatal rats,which may be related to the down-regulation of MMP-9 expression,pro BDNF and mB DNF conversion disorder in hippocampus and the apoptosis of hippocampal neurons.However,single exposure to propofol has no significant effect.