Propofol exposure in early pregnancy impairs learning and memory increases histone deacetylase in the offspring rats / 医学研究生学报

ABSTRACT

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 the 5th 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.