摘要
目的孕期母体丙泊酚暴露对子代学习记忆有明显的损害作用,然而其具体机制尚未明确。文中旨在探讨孕早期母体丙泊酚暴露对子代大鼠学习记忆功能以及组蛋白去乙酰化酶2(HDAC2)的影响。方法取孕5~7 d的SD大鼠20只,采用随机数表法随机分为对照组(等渗盐水)和丙泊酚组(丙泊酚),每组10只。子鼠出生后,丙泊酚组每只母鼠所产子鼠分为丙泊酚SAHA组(n=50,注射90 mg/kg HDAC抑制剂SAHA)和丙泊酚溶媒组(n=47,注射等量溶媒DMSO);对照组每只母鼠所产子鼠分为对照SAHA组(n=48,注射90 mg/kg SAHA)和对照溶媒组(n=45,注射等量溶媒DMSO)。各组进行Morris水迷宫实验。处死后取海马组织,采用免疫荧光法检测HDAC2蛋白的表达水平。结果丙泊酚溶媒组水迷宫实验第5、6天子鼠逃避潜伏期[(65.93±30.42)、(50.72±24.72)s]较对照溶媒组[(29.32±16.38)、(21.34±13.79)s]、丙泊酚SAHA组[(42.52±20.43)、(24.28±13.41)s]明显延长,穿越平台次数减少(P<0.05)。丙泊酚溶媒组HDAC2蛋白表达水平(1.37±0.03)较对照溶媒组(1.00±0.02)、丙泊酚SAHA组(1.08±0.02)明显升高(P<0.05)。结论孕早期丙泊酚暴露可引起子代大鼠学习记忆功能损害,其机制与上调子代大鼠海马区HDAC2蛋白表达有关。
Objective Propofol exposure during pregnancy impairs learning and memory of the offspring rats,but its definite mechanisms are not yet clear. This study is to assess the impact of propofol exposure during early pregnancy on the learning,memory,and the expression of histone deacetylase 2（HDAC2） in the hippocampus of the offspring rats. Methods Twenty Sprague-Dawley rats at gestation days 5-7,weighing 270-320 g,were equally randomized into a propofol exposure and a saline control group. The offspring rats of the former group were again divided into a propofol SAHA（n = 50） and a propofol DMSO group（n = 47）,and those of the latter into a control SAHA（n = 48） and a control DMSO group（n = 45）. On postnatal day 30,the offspring rats were subjected to the Morris water maze（MWM） test at 2 hours after intraperitoneally injected with the HDAC inhibitor subcroylanilide hydroxamic acid（SAHA） at 90 mg/kg and equal volume of dimethyl sulfoxide（DMSO）,respectively. Then all the animals were sacrificed and the hippocampal tissue harvested for determination of the expression of the HDAC2 protein by immunofluorescence staining. Results On the5 th and 6th days of the MWM test,the escape latency was significantly prolonged in the propofol DMSO group（[65. 93 ± 30. 42] and[50.72±24.72] s） as compared with the control DMSO（[29.32±16.38] and [21. 34 ± 13. 79] s） and the propofol SAHA group（[42.52±20.43]and [24.28±13.41]s）（P〈0.05）,while the platform-crossing frequency was markedly lower in the former than in the latter two groups（P〈0.05）. The expression of the HDAC2 protein remarkalby up-regulated in the propofol DMSO group（1.37±0.03）in comparison with the control DMSO（1.00±0.02） and the control SAHA group（0.99±0.03）（P〈0.05）. Conclusion Propofol exposure in early pregnancy impairs learning and memory of the offspring rats,which is associated with the up-regulated expression of the HDAC2 protein in the hippocampus.
出处
《医学研究生学报》
CAS
北大核心
2017年第8期804-807,共4页
Journal of Medical Postgraduates
基金
国家自然科学基金(81460175)
