基础医学与临床 ›› 2022, Vol. 42 ›› Issue (1): 89-93.

• 研究论文 • 上一篇    下一篇

GSK650394对慢性应激抑郁症模型大鼠行为及海马神经营养的调节作用

刘丹1,蔺晓源1,杨蕙2,刘彤彤3,刘平安3,孟盼3   

  1. 1. 湖南中医药大学 第一附属医院
    2. 湖南中医药大学第一附属医院
    3. 湖南中医药大学
  • 收稿日期:2020-09-11 修回日期:2021-06-29 出版日期:2022-01-05 发布日期:2022-01-05
  • 通讯作者: 孟盼 E-mail:mengpan0822@163.com
  • 基金资助:
    湖南省自然科学基金优秀青年项目;湖南省自然科学基金青年项目;湖南省教育厅优秀青年项目;湖南中医药大学中医学国内一流建设学科开放基金

Regulating effects of GSK650394 on behavior and hippocampal neurotrophy in chronic stress model of depression in rats

  • Received:2020-09-11 Revised:2021-06-29 Online:2022-01-05 Published:2022-01-05

摘要: 目的 探讨SGK1抑制剂GSK650394对抑郁症模型大鼠抑郁样行为及海马神经营养的调节作用。方法 将SD大鼠随机分为3组,即空白对照、抑郁模型、GSK650394组,采用慢性温和不可预见性应激加孤养的方式建立抑郁模型,造模同时腹腔注射给药,采用强迫游泳、糖水消耗、Morris水迷宫实验观察模型动物的情绪行为变化,Elisa分别观察大鼠海马血浆和血清中CORT、单胺神经递质的变化,采用Western-Blotting方法检测海马中BDNF、NT-3、NGF的表达。结果 与空白组比较,模型组大鼠蔗糖水偏食度显著降低、游泳不动时间增加(P﹤0.01),EL、Lat.T均显著延长(P﹤0.05或P﹤0.01),血浆CORT显著升高(P﹤0.01),血清5-HT、NE和海马NT-3、BDNF、NGF表达显著降低(P﹤0.05或P﹤0.01);与模型组比较,GSK650394可显著增加蔗糖水偏食度、降低游泳不动时间(P﹤0.05或P﹤0.01),缩短EL、Lat.T(P﹤0.05),降低血浆CORT的含量(P﹤0.01),增加血清5-HT、NE的含量(P﹤0.05或P﹤0.01),促进海马NT-3、BDNF、NGF的表达(P﹤0.05)。结论 SGK1抑制剂可显著缓解抑郁样行为,其机制可能与促进神经营养有关。

关键词: 关键词:抑郁症, SGK1, GSK650394, 海马, 神经营养

Abstract: Objective To investigate the protective effect of SGK1 inhibitor GSK650394 on depressive behavior and hippocampal neurotrophy in depressive rats. Methods SD rats were randomly divided into control group, depression model group and GSK650394 group. Depression model was established by chronic mild unpredictable stress. The behavioral changes of the SD rats were observed by novel feeding test, forced swimming and 1% sugar consumption test. The changes of CORT and monoamine neurotransmitters in plasma and serum were observed by Elisa. The changes of BDNF, NT-3 and NGF in hippocampus were detected by Western-Blotting. Results Compared with the control group, sucrose preference decreased and swimming immobility time increased significantly (P < 0.01), EL and Lat.T prolonged significantly (P < 0.05 or P < 0.01), the content of CORT in plasma increased significantly (P < 0.01), the content of 5-HT, NE in serum and the expression of BDNF, NT-3, NGF in hippocampus was significant increased in the model group. Compared with model group, GSK650394 significantly increased sucrose preference, decreased immobility time (P < 0.05 or P < 0.01), shortened EL and Lat.T (P < 0.05), decreased the content of CORT in plasma (P < 0.01), increased the level of 5-HT and NE in serum (P < 0.01), promoted the expression of NT-3, BDNF and NGF in hippocampus. Conclusion SGK1 inhibitor can significantly relieve depression like behavior, which may be related to promoting neurotrophin.

Key words: Key words: depression, SGK1, GSK650394, hippocampus, neurotrophin

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