异丙酚暴露对老年大鼠的认知功能和组蛋白去乙酰化酶的影响

Effects of propofol exposure on cognitive function and histone deacetylase in aged rats

目的探讨异丙酚暴露对老年大鼠的认知功能和组蛋白去乙酰化酶(HDAC)的影响。方法选取健康雄性Wistar大鼠30只,通过随机数表法将大鼠分为对照组、实验组及空白组,每组10只大鼠。空白组于正常环境下喂养,对照组给予异丙酚注射后注入90 mg/kg等渗溶媒,实验组给予异丙酚注射后注入90 mg/kg HDAC抑制剂。用Morris水迷宫实验记录逃避潜伏期评估大鼠认知功能,干预结束后分离脑组织使用免疫荧光法检测HDAC蛋白的表达水平,并采用酶联免疫吸附试验测定脑细胞因子[肿瘤坏死因子α(TNF-α)、缺氧诱导因子1α(HIF-1α)、脑源性神经营养因子(BDNF)、血管内皮生长因子(VEGF)]的含量。结果干预后1、3、5 d,实验组及对照组潜伏期均高于空白组,但实验组潜伏期低于对照组,差异均有统计学意义(P<0.05)。实验组及对照组跨格数、直立次数及中央区域停留时间均高于空白组,但实验组低于对照组,差异均有统计学意义(P<0.05)。实验组及空白组HDAC含量均低于对照组,且实验组低于空白组,差异均有统计学意义(P<0.05)。实验组、对照组大鼠脑组织中TNF-α的含量显著高于空白组,HIF-1α、BDNF、VEGF的含量显著均低于空白组,但实验组TNF-α的含量显著低于对照组,HIF-1α、BDNF和VEGF的含量均显著高于对照组,差异均有统计学意义(P<0.05)。结论异丙酚暴露损害老年大鼠的认知功能,升高HDAC水平,使用HDAC抑制剂后可有效改善异丙酚暴露所致认知功能。

Objective To explore the effects of propofol exposure on cognitive function and histone deacetylase(HDAC)in old rats.Methods Thirty healthy male Wistar rats were selected and divided into control group,experimental group and blank group by random number table method,with 10 rats in each group.The blank group was fed under normal environment,the control group was injected with 90 mg/kg isotonic vehicle after propofol injection,and the experimental group was injected with 90 mg/kg HDAC inhibitor after propofol injection.The escape latency was recorded by Morris water maze test to evaluate the cognitive function of rats.After the intervention,brain tissues were isolated to detect the expression level of HDAC protein by immunofluorescence,and the content of brain cytokines[tumor necrosis factorα(TNF-α),hypoxia inducible factor 1α(HIF-1α),brain-derived neurotrophic factor(BDNF)and vascular endothelial growth factor(VEGF)]were determined by ELISA.Results At 1,3,5 days after intervention,the latency of the experimental group and the control group was higher than that of the blank group,but the latency of the experimental group was lower than that of the control group,the differences were statistically significant(P<0.05).The number of straddles,the number of standing up and the stay time in the central area in the experimental group and the control group were higher than those in the blank group,but those in the experimental group were lower than those in the control group,the differences were statistically significant(P<0.05).The content of HDAC in the experimental group and the blank group was lower than that of the control group,and that in the experimental group was lower than that in the blank group,the differences were statistically significant(P<0.05).The content of TNF-αin brain tissue of rats in experimental group and control group was significantly higher than that in the blank group,the contents of HIF-1α,BDNF and VEGF in the experimental group and control group were significantly lower than those in the blank group,but the content of TNF-αin the experimental group was significantly lower than that in the control group,the contents of HIF-1α,BDNF and VEGF in the experimental group were significantly higher than those in the control group,the differences were statistically significant(P<0.05).Conclusion Propofol exposure impairs the cognitive function of elderly rats and increases the level of HDAC.The use of HDAC inhibitors can effectively improve the cognitive function caused by propofol exposure.