JAK2-STAT3信号通路在天麻素改善小鼠抑郁样行为中的作用研究  

Gastrodin Ameliorates Depression-like Behavior of Mice through JAK2-STAT3 Signaling Pathway

作　　者：王上 董文娟 刘鹏亮 杨根梦 沈宝玉 于浩 张冬先 李利华 洪仕君 WANG Shang;DONG Wen-juan;LIU Peng-liang;YANG Gen-meng;SHEN Bao-yu;YU Hao;ZHANG Dong-xian;LI Li-hua;HONG Shi-jun(The School of Forensic Medicine,Kunming Medical University,Kunming,Yunnan,650500,China)

机构地区：[1]昆明医科大学法医学院,云南昆明650500

出　　处：《现代生物医学进展》2021年第19期3622-3627,共6页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81760337,81560302);云南省科技厅-昆明医科大学联合专项(2017FE467-003);云南省创新团队项目(2017HC007)。

摘　　要：目的:观察天麻素对小鼠抑郁症模型异常行为的改善以及Janus激酶2-信号转导和转录激活因子3(JAK2-STAT3)信号通路的表达变化。方法:40只雄性昆明小鼠,随机分为正常组和模型组。模型组小鼠经过4周CUMS刺激建模,第6周检测小鼠行为学变化以验证建模效果。随后将模型组分为CUMS+生理盐水、CUMS+氟西汀以及CUMS+天麻素3个亚组,第7-8周继续进行CUMS刺激,同时对3个亚组小鼠腹腔注射给药。第9周再次进行行为学检测。取小鼠脑组织进行HE染色(hematoxylin-eosin staining)和蛋白免疫印迹(western blot)检测。结果:第6周检测结果显示:与对照组比较,模型组小鼠体重增幅显著降低(P<0.001),悬尾和强迫游泳不动时间显著增加(P<0.001、P<0.001),糖水消耗率显著降低(P<0.001)。第9周检测结果显示:与CUMS+生理盐水组相比,CUMS+氟西汀组和CUMS+天麻素组小鼠体重增幅显著增加(P<0.001,P<0.001),强迫游泳不动时间显著降低(P<0.001,P<0.001),悬尾不动时间显著降低(P<0.01,P<0.01),糖水消耗率显著增加(P<0.001、P<0.001)。与CUMS+生理盐水组比较,CUMS+天麻素组小鼠JAK2、STAT3、IL-1β蛋白表达显著降低(P<0.01、P<0.01、P<0.05);HE染色结果提示,CUMS+生理盐水组小鼠神经元形态发生改变,细胞结构不清晰,细胞核固缩、深染;与CUMS+生理盐水组相比,CUMS+天麻素组小鼠神经元形态得到改善。结论:天麻素可以有效改善CUMS诱导的小鼠抑郁样行为,其作用可能与JAK2-STAT3信号通路关键蛋白的表达有关。Objective:To observe the effects of gastrodin on the abnormal behaviors and the expressions of janus kinase 2-signal transducer and transcription activator 3(JAK2-STAT3)signaling pathway in depression mice model.Methods:Forty male Kunming mice,were randomly divided into normal and model groups.After 4 weeks CUMS stimulation,the behavioral changes of mice were detected in week 6 to verify the modeling effect.The model was then composed of three subgroups:CUMS+saline,CUMS+fluoxetine and CUMS+gastrodin group,CUMS stimulation continued during weeks 7-8.At the same time,three subgroups of mice were injected intraperitoneally.The behavior test was carried out again in week 9.Mouse brain tissue was HE stained and Western blot.Results:The results of week 6 showed that,compared to control group,CUMS stimulation significantly decreased the weight change(P<0.001),increased the immobility time in tail suspension and forced swimming test(P<0.001,P<0.001)and decreased the percentage of sucrose intake(P<0.001).At week 9,the results showed:compared to CUMS+saline group,CUMS+fluoxetine group and CUMS+gastrodin group significantly increased weight change(P<0.001,P<0.001),decreased the immobility time in forced swimming test(P<0.001,P<0.001),decreased immobility the time in tail suspention test(P<0.01,P<0.01)and increased the percentage of sucrose intake(P<0.001,P<0.001).Compared with CUMS+saline group,the expression of JAK2,STAT3、IL-1βin CUMS+gastrodin group decreased significantly(P<0.01,P<0.01,P<0.05);The results of HE staining showed that,the morphology of neurons in CUMS+saline group was changed,the cell structure was not clear,the nucleus shrank and dyed deeply,and the morphology of neurons in CUMS+gastrodin group was improved compared to that in CUMS+saline group.Conclusion:Gastrodin could effectively improve the CUMS induced depressive behaviors in mice,and its effect might be related to the expressions of key proteins in JAK2-STAT3 signaling pathway.

关 键 词：慢性不可预测轻度应激 天麻素 JANUS激酶2 信号转导和转录激活因子3 

分 类 号：R-33[医药卫生] R749