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.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[J].,2021,(19):3622-3627 |
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 |
投稿时间:2021-03-31 修订日期:2021-04-27 |
DOI:10.13241/j.cnki.pmb.2021.19.005 |
中文关键词: 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 |
英文关键词: Chronic unpredictable mild stress (CUMS) Gastrodin Janus kinase 2 (JAK2) Signal transducer and transcription activator 3 ( STAT3) |
基金项目: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) |
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中文摘要: |
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。 |
英文摘要: |
ABSTRACT 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-1β in 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. |
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