异丙酚对大鼠大脑功能和TPA、MMP9表达的影响

发布时间：2018-11-28 08:26

【摘要】：目的:探讨异丙酚对新生大鼠海马组织型纤溶酶原激活物(tissue-type plasminogen activator,tPA)和基质金属蛋白酶9(matrix metalloproteinase 9,MMP9)表达的影响及其与认知功能的关系。方法:新生7日龄大鼠随机分为3组:对照(CON)组为连续7 d腹腔注射生理盐水;异丙酚单次麻醉(SP)组为连续腹腔注射生理盐水6d,第7天注射异丙酚;异丙酚多次麻醉(RP)组为连续7 d腹腔注射异丙酚。各组随机取6只大鼠行血糖和血气监测。于建模后2 h、24 h、48 h、72 h和30 d各组随机取大鼠分离海马组织。其余大鼠喂养至出生后25 d行Morris水迷宫实验,测定其空间学习记忆能力。HE染色及尼氏染色观察海马形态学改变。采用Western blot法检测tPA和MMP9蛋白表达的动态变化,RT-PCR法测定tPA和MMP9的mRNA表达改变。结果:与CON组相比,RP组各时点大鼠海马tPA和MMP9蛋白表达均呈明显的下降趋势(P0.05);而SP组仅24 h时tPA表达呈下降趋势,其它时点下降趋势不明显,MMP9表达均无明显下降。与CON组相比,24 h时RP组海马tPA及MMP9的mRNA表达明显下调(P0.05),而SP组下调不明显。Morris水迷宫实验第3天开始RP组的逃逸潜伏期较CON组和SP组延长(P0.05),且RP组在原平台象限的探索时间及穿越原平台所在位置的次数较CON组和SP组减少(P0.05),而CON组和SP组之间的差异无统计学显著性。与CON组相比,RP组海马神经细胞数量减少且排列紊乱,神经元内尼氏体明显减少,部分神经元出现变性及坏死。而SP组与CON组相比差异无统计学显著性。结论:多次异丙酚麻醉可导致新生大鼠远期认知功能障碍,其机制可能与海马tPA及MMP9的表达下调、海马神经元正常形态及功能破坏有关;而单次异丙酚麻醉无此作用。
[Abstract]:Aim: to investigate the effects of propofol on the expression of tissue plasminogen activator (tissue-type plasminogen activator,tPA) and matrix metalloproteinase-9 (MMP9) in hippocampus of neonatal rats and the relationship between propofol and cognitive function. Methods: rats of 7 days old were randomly divided into three groups: control group (CON) group) received intraperitoneal injection of saline for 7 days, propofol single anesthesia group (SP) group) received intraperitoneal injection of normal saline for 6 days, and propofol on day 7. Propofol was injected intraperitoneally for 7 days in (RP) group. Six rats were randomly selected for blood glucose and blood gas monitoring. Hippocampal tissues were randomly isolated from rats in each group for 72 h and 30 d at 24 h and 48 h after modeling. The other rats were fed until 25 days after birth for Morris water maze test to determine their spatial learning and memory ability. The morphological changes of hippocampus were observed by HE staining and Nissl staining. The dynamic changes of tPA and MMP9 protein expression were detected by Western blot and mRNA expression of tPA and MMP9 was detected by RT-PCR assay. Results: compared with CON group, the expression of tPA and MMP9 protein in hippocampus of RP group decreased significantly at all time points (P0.05). However, in SP group, the expression of tPA decreased at 24 h, but not at other time points. The expression of MMP9 did not decrease significantly at other time points. Compared with CON group, the mRNA expression of tPA and MMP9 in hippocampus of RP group was significantly decreased at 24 h (P0.05), while that of SP group was not significantly down-regulated. The escape latency of RP group was longer than that of CON group and SP group since the 3rd day of Morris water maze experiment (P0.05). The exploration time of RP group in the original platform quadrant and the times of crossing the original platform location decreased compared with CON group and SP group (P0.05), but there was no significant difference between CON group and SP group. Compared with CON group, the number of hippocampal neurons in RP group was decreased and the number of hippocampal neurons was disordered, the Nissl bodies in neurons were decreased obviously, and some neurons were denatured and necrotized. There was no significant difference between SP group and CON group. Conclusion: multiple propofol anesthesia may lead to long-term cognitive impairment in neonatal rats. The mechanism may be related to the down-regulation of tPA and MMP9 expression in hippocampus and the normal morphology and function of hippocampal neurons, but the single propofol anesthesia has no such effect.
【作者单位】：重庆医科大学附属第一医院麻醉科;
【基金】：卫生部国家临床重点专科建设项目[财社(2011)170号] 重庆市卫生局医学科研计划(No.2012-1-018)
【分类号】：R726.1

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