FH/Wjd大鼠与SD大鼠焦虑易感性比较  

Comparison of anxiety susceptibility between FH/Wjd rats and SD rats

作　　者：熊庭旺 吴芹 刘杰 刘波 徐云燕 王丽娜 张玮 张成宸 石京山 XIONG Ting-wang;WU Qin;LIU Jie;LIU Bo;XU Yun-yan;WANG Li-na;ZHANG Wei;ZHANG Cheng-chen;SHI Jing-shan(Key Lab of Basic Pharmacology of Ministry of Education and Joint International Research Lab of Ethnomedicine of Ministry of Education,Zunyi Medical University, Zunyi, Guizhou 563099, China)

机构地区：[1]遵义医科大学基础药理教育部重点实验室,特色民族药国际合作联合实验室,贵州遵义563099

出　　处：《中国药理学通报》2020年第5期722-726,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81473201,81773739);贵州省教育厅石京山药理学导师工作室[No GZS-2016(7)]。

摘　　要：目的以SD大鼠为对照,观察FH/Wjd大鼠是否具有焦虑易感性。方法高架十字迷宫、旷场实验检测SD大鼠、FH/Wjd大鼠焦虑行为;高效液相色谱电化学技术检测皮层DA、5-HT及其代谢产物的含量,并计算DA、5-HT的代谢率;ELISA检测皮层COMT、MAO活性及CORT、ACTH含量;PCR检测不同部位COMT mRNA的表达,mRNA-seq检测海马组织中所有基因的表达。结果与SD大鼠比较,FH/Wjd大鼠在高架十字迷宫闭合臂中运动距离及活动总距离均显著提高;旷场中央区域活动路程明显较低,活动总路程显著较高;DA、5-HT、DOPAC含量较低,HVA、5-HIAA含量无明显差异;FH/Wjd大鼠HVA/DA、5-HIAA/5-HT比值,COMT、MAO活性,CORT、ACTH含量,COMT mRNA的表达均显著高于SD大鼠;FH/Wjd大鼠与SD大鼠的差异基因主要富集在神经活性受体配体途。结论与SD大鼠比较,FH/Wjd大鼠中枢DA、5-HT含量低下、其代谢亢进,HPA轴亢进,COMT表达异常,神经精神系统可能存在异常。FH/Wjd大鼠较之SD大鼠,具有明显的焦虑特性。Aim With SD rats as control,to observe the anxiety susceptibility of FH/Wjd rats.Methods The anxiety behavior of 3-month-old SD rats and age-matched FH/Wjd rats were evaluated by elevated plus-maze test and open field test.The contents of 5-hydroxytryptamine(5-HT),dopamine(DA)and its metabolite from the cortex were detected by high performance liquid chromatography with electrochemical detection,and the metabolic ratios of DA and 5-HT were calculated.The activities of catechol-O-methyltransferase(COMT)and monoamine oxidase(MAO),the contents of corticosterone(CORT)and adrenocorticotropic hormone(ACTH)were detected by enzyme-linked immunosorbent assay in cortex.The expression of COMT was detected by polymerase chain reaction.The expression of all genes hippocampus was detected by mRNA-seq.Results As compared with SD rats,in FH/Wjd rats,the closed arms′distance and the total distance were significantly higher in elevated plus-maze;the central distance was significantly shorter,and the total distance was significantly longer in open field.The contents of DA,5-HT and DOPAC in cortex were significantly lower,and there was no significant difference in HVA and 5-HIAA.The ratio of HVA/DA and 5-HIAA/5-HT,the activity of COMT and MAO,the level of CORT and ACTH,the mRNA expression of COMTwere all higher.The differential genes of FH/Wjd rats and SD rats were mainly enriched in the neuroactive ligand-receptor interaction pathway.Conclusions Compared with SD rats,FH/Wjd rats have lower DA and 5-HT contents,hypermetabolism,hyperactivity of hypothalamic-pituitary-adrenal axis,abnormal expression of COMT and gene encoding neuropsychiatric system.Therefore,FH/Wjd rats have obvious anxiety characteristics.

关 键 词：FH/Wjd大鼠 SD大鼠 焦虑 多巴胺 5-羟色胺 HPA轴 COMT MRNA-SEQ 

分 类 号：R-332[医药卫生] R322.81