基于慢性不可预知性温和刺激大鼠模型的前额叶皮质谷氨酸系统及肠道菌群在抑郁症发病机制中的作用  

Prefrontal cortex EAAT2 levels in the pathogenesis of depression in a rat model of chronic unpredictable mild stress

作　　者：毛俊雄 马琦[1,2] 彭朕磊 安治国 罗晓[1] 孙乐乐[1] 史新玉 杜雯 靳路[1] 高帅帅 景琳霞 蒋世洁 伊琦忠 MAO Junxiong;MA Qi;PENG Zhenlei(Xinjiang Clinical Research Center for Mental(Psychological)Disorders,Psychological Medicine Center,the First Affiliated Hospital of Xinjiang Medical University,Urumqi,830054,China)

机构地区：[1]新疆医科大学第一附属医院,新疆精神(心理)临床医学研究中心,省部共建中亚高发病成因与防治国家重点实验室,乌鲁木齐830054 [2]新疆医科大学第一附属医院临床医学研究院

出　　处：《国际精神病学杂志》2024年第2期372-377,381,共7页Journal Of International Psychiatry

基　　金：新疆维吾尔自治区自然科学基金(编号:2022D01D6);国家自然科学基金(编号:81960258)。

摘　　要：目的用慢性不可预知性温和刺激范式构建抑郁障碍大鼠模型,检测前额叶氨基酸转运蛋白2(EAAT2)和谷氨酸水平及肠道菌群分布,探索它们在抑郁症发病中的作用。方法将40只SD大鼠随机分为对照组、抑郁组及干预组氟西汀(Flu)和乳酸菌素(Lac)组。对照组大鼠正常饲养,其余三组建模4周,造模成功后抑郁组继续温和刺激,氟西汀组和乳酸菌素组在慢性温和刺激基础上分别加用乳酸菌素片和氟西汀灌胃干预两周。于第4周、第6周进行行为学评价;第6周后检测大鼠前额叶皮质谷氨酸、eaat2 mRNA及蛋白表达量,并分析其肠道菌群。结果抑郁组前额叶皮质谷氨酸含量高于对照组和干预组(P<0.05),eaat2 mRNA及蛋白水平低于对照和干预组(P<0.05);四组大鼠的肠道优势菌群各不相同。结论eaat2 mRNA、EAAT2、谷氨酸水平及肠道微生态可能在慢性不可预知性温和刺激范式大鼠模型的抑郁样行为的发生中发挥着重要作用。Objective Major depressive disorder rat model was constructed by chronic unpredictable mild stress.The levels of excitatory amino acid transporter 2,glutamate in frontal lobe and the distribution of gut microbiota were detected,and to explore their relationship with the pathogenesis of MDD.Methods Forty SD rats were randomly divided into control group,depression group,intervention group(Lac group and Flu group).Control group were fed normally,and others were build molds for 4 weeks.After successful modeling,mild stress continued in the MDD group,Lac and Flu group were supplemented with lactobacillin tablets and fluoxetine for two weeks.The behavior of the rats was evaluated at 4th and 6th week.The content of glutamate,eaat2 mRNA and protein expression were detected,and gut microbiota was analyzed.Results The content of glutamate of depression group was higher than control and intervention group(P<0.05),and mRNA and protein levels of eaat2 were lower(P<0.05).The dominant microbiota of all groups was different.Conclusion Gut microbiota,EAAT2 and glutamate level may play an important role in depression-like behavior.

关 键 词：抑郁障碍 前额叶皮质 谷氨酸 EAAT2 肠道菌群 

分 类 号：R749.4[医药卫生—神经病学与精神病学]