人参调节海马星形胶质细胞兴奋性氨基酸转运功能拮抗小鼠应激障碍的研究

Stress-Induced Dysfunction of Excitatory Amino Acid Transport in Hippocampal Astrocytes of Mice

目的观察应激对小鼠海马星形胶质细胞兴奋性氨基酸转运功能的影响,并探讨人参水煎液对此功能紊乱的调节作用。方法100只雄性ICR小鼠随机分为10组,对照组和模型组各5组。应激模型采用腹腔注射皮质酮,10组动物分配至5个时间点(1、2、3、4、5周)进行实验。另取30只雄性ICR小鼠分为对照组、模型组和人参干预组,每组10只。2组实验独立开展,实验周期均为5周。实验结束后,检测体质量、行为学、神经元结构/功能指标(NF-L、SYP)、星形胶质细胞生物标志指标(GFAP)和兴奋性氨基酸转运功能指标(EAATs),进行统计学分析。结果皮质酮注射1~3周小鼠海马星形胶质细胞标志蛋白反应性高表达,第3周末表达水平下调(P<0.05),同时神经元结构功能指标表达下调提示神经元损伤,实验动物出现体质量和行为学的显著改变(P<0.05)。进一步检测星形胶质细胞兴奋性氨基酸转运蛋白,显示表达下调,并与神经元损伤呈正相关性。人参干预组对模型小鼠EAATs、GFAP、NF-L和SYP的表达下降均有显著改善作用(P<0.05)。结论腹腔注射皮质酮可使小鼠海马神经元损伤并出现行为学异常,其机制可能是应激影响星形胶质细胞兴奋性氨基酸转运功能所导致,人参水煎液可通过此机制发挥抗应激作用。

OBJECTIVE To observe the effect of stress on the excitatory amino acid transport function of hippocampus astrocytes in mice.METHODS 100 male ICR mice were randomly divided into 10 groups,5 control groups and 5 model groups.The stress model was made by intraperitoneal injection of corticosterone.Ten groups of animals were allocated to five time points(1,2,3,4,5 weeks).Another 30 male ICR mice were divided into control group,model group and ginseng intervention group.Two groups of experiments were conducted independently,and the experimental period was 5 weeks.At the end of the experiment,body weight,ethology,neuron structure/function index(NF-L,SYP),astrocyte biomarker index(GFAP)and excitatory amino acid transport function index(EAATs)were measured and analyzed statistically.RESULTS The expression of astrocyte marker protein was highly expressed in the hippocampus of mice 1 to 3 weeks after corticosterone injection.The expression level was down-regulated at the 3 rd week and showed a significant difference(P<0.05),and the expression of neuronal structural function index was down-regulated.Neuronal damage,experimental animals showed significant changes in body weight and behavior(P<0.05).Further detection of astrocyte excitatory amino acid transporter protein showed down-regulation of expression and a positive correlation with neuronal damage.CONCLUSION Intraperitoneal injection of corticosterone can damage the hippocampus neurons of mice and exhibit behavioral abnormalities.The mechanism may be caused by stress affecting the astrocyte excitatory amino acid transport function.