Abstract: Objective To investigate the mechanism of the activation of Astrocytes on the cognitive impairment induced by propofol in aged rats.Methods The rat model was established by intraperitoneal injection of PPF.The animal experiment was divided into a control group and a model group,and the animals were divided into three subgroups based on the time of sacrifice:1d,3d,and 7d.New object recognition experiments and jumping platform maze experiments was used to evaluate the spatial learning and memory abilities of rats in each group.The apoptosis rate of neurons in rat hippocampal tissue,the levels of tumor necrosis factor-a (TNF-α) and interleukin-6 (IL-6) in serum,the mitochondrial membrane potential,the ATP levels,and the expression of lial fibrillary acidic protein (GFAP) and brain derived neurotrophic factors (BDNF)were detected.Results Compared with the Control group rats at the same time point,the discrimination index and latency,the mitochondrial membrane potential,the ATP levels,and the expression of BDNF in brain tissue were significantly decreased in the Model group rats at 1 day,3 days,and 7 days,while the number of errors,the apoptosis rate of neurons,the levels of TNF-α and IL-6 in serum,and the expression of GFAP in brain tissue were significantly increased.The differences were statistically significant (all P＜0.05).Model intra group analysis showed that compared with rats at the 1-day time point,the discrimination index and latency,the mitochondrial membrane potential,the ATP levels,and the expression of BDNF in brain tissue were significantly decreased in the 3 days,while the number of errors,the apoptosis rate of neurons,the levels of TNF-α and IL-6 in serum,and the expression of GFAP in brain tissue were significantly increased.Compared with rats at the 3-day time point,the discrimination index and latency,the mitochondrial membrane potential,the ATP levels,and the expression of BDNF in brain tissue were significantly increased in the 7 days,while the number of errors,the apoptosis rate of neurons,the levels of TNF-α and IL-6 in serum,and the expression of GFAP in brain tissue were significantly decreased.The differences were statistically significant (all P＜0.05).Conclusion In the cognitive impairment model induced by PPF in aged rats,Astrocytes were in an activated state.On the one hand,their activation could upregulate the levels of inflammatory mediators TNF-α and IL-6,promoting the development of inflammatory stress.On the other hand,it could significantly increase the expression of BDNF,improve mitochondrial dysfunction of neuronal cells,and demonstrate the protective effect of neuronal cells.

Key words: Astrocytes, Activation, Propofol, Aged rats, Cognitive impairment

摘要： 目的 探讨星型胶质细胞的活化对丙泊酚(propofol,PPF)诱导的老年大鼠认知功能障碍的影响机制。方法 通过腹腔注射PPF构建大鼠模型,动物实验分为对照组和模型组,在根据处死动物时间分为1 d、3 d、7 d 三个亚组。新物体识别实验和跳台迷宫实验评估各组大鼠空间学习和记忆能力;检测大鼠海马组织中的神经元的细胞凋亡率、血清中肿瘤坏死因子(tumornecrosis factor-a,TNF-α)和白介素-6(interleukin-6,IL-6)的水平、线粒体膜电位、ATP的水平、AS活化相关蛋白胶质纤维酸性蛋白(lial fibrillary acidic protein,GFAP)和脑源性神经营养因子(brain derived neurotrophic factors,BDNF)的表达。结果 与同时点的对照组大鼠相比,模型组大鼠1 d、3 d、7 d的辨别指数和潜伏期、线粒体膜电位、ATP的水平、脑组织中BDNF的表达明显下降,错误次数、神经元的细胞凋亡率、血清中TNF-α和IL-6的水平、脑组织中GFAP的表达明显升高,差异均具有统计意义(均P＜0.05);;模型组内分析显示,与1 d时间点的大鼠相比,3 d时间点的大鼠辨别指数和潜伏期、线粒体膜电位、ATP的水平、脑组织中BDNF的表达明显下降,错误次数、神经元的细胞凋亡率、血清中TNF-α和IL-6的水平、脑组织中GFAP的表达明显升高,与3 d时间点的大鼠相比,7 d时间点的大鼠辨别指数和潜伏期、线粒体膜电位、ATP的水平脑组织中BDNF的表达明显升高,错误次数、神经元的细胞凋亡率、血清中TNF-α和IL-6的水平、脑组织中GFAP的表达明显下降,差异均具有统计意义(均P＜0.05)。结论 在PPF诱导的老年大鼠认知障碍模型中,星型胶质细处于活化状态,其活化一方面上调炎症性介质TNF-α和IL-6的水平,推动炎症性应激的发展,另一方面能明显升高BDNF的表达,改善神经元细胞的线粒体功能障碍,显示了神经元细胞保护的作用。

关键词: 星型胶质细胞, 活化, 丙泊酚, 老年大鼠, 认知功能障碍