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中国应用生理学杂志 ›› 2020, Vol. 36 ›› Issue (4): 354-357.doi: 10.12047/j.cjap.5936.2020.076

• 研究论文 • 上一篇    下一篇

加味逍遥散对LPS诱导的抑郁模型大鼠海马小胶质细胞TLR4/NF-κB通路的影响*

郭锐1△, 秦卫帅1, 张双勇1, 张淑玲2   

  1. 1.郑州市中医院脑病一科, 河南 郑州 450007;
    2.郑州市人民医院神经内科, 河南 郑州 450003
  • 收稿日期:2019-09-10 修回日期:2020-06-16 发布日期:2020-11-09
  • 通讯作者: Tel: 13598088527; E-mail: uhfyj92@163.com
  • 基金资助:
    *河南省医学科技管管计划项目(2018020821)

Effects of modified Xiaoyao San on TLR4/NF-κB pathway in hippocampal microglia of LPS-induced depression model rats

GUO Rui1△, QIN Wei-shuai1, ZHANG Shuang-yong1, ZHANG Shu-ling2   

  1. 1. Department of Encephalopathy, Zhengzhou Chinese Medicine Hospital, Zhengzhou 450007;
    2. Department of Neurology, Zhengzhou People ’s Hospital, Zhengzhou 450003, China
  • Received:2019-09-10 Revised:2020-06-16 Published:2020-11-09

摘要: 目的: 观察加味逍遥散对LPS诱导的抑郁模型大鼠海马小胶质细胞TLR4/NF-κB通路的影响,探讨其抗抑郁机制。方法: 将SD大鼠随机分为对照组、模型组、氟西汀组(10.8 mg·kg-1)、加味逍遥散低、高剂量组(3.64、7.28 g·kg-1)。采用慢性LPS注射(ip,0.5 mg·kg-1)的方法建立抑郁大鼠模型,于造模同时灌胃给药,共14 d。采用旷场和强迫游泳实验评价大鼠的抑郁样行为,免疫组化法检测海马小胶质细胞标志蛋白Iba-1的表达,ELISA法检测海马匀浆液中TNF-α、IL-6的含量,Western blot法检测海马TLR4、NF-κB蛋白的表达。结果: 与对照组比较,模型组大鼠抑郁样行为显著(P<0.01),海马小胶质细胞明显激活(P<0.01),TNF-α、IL-6含量增加(P<0.01),TLR4、NF-κB蛋白明显上调(P<0.01);与模型组比较,氟西汀和高剂量加味逍遥散组大鼠抑郁样行为明显缓解(P< 0.05),小胶质细胞Iba-1表达恢复正常(P<0.01),TNF-α、IL-6含量下降(P<0.01),TLR4、NF-κB蛋白表达下调(P<0.05);与氟西汀组比较,高剂量加味逍遥散组各指标无统计学差异,提示两者抗抑郁功效无显著区别。结论: 加味逍遥散能明显改善大鼠的抑郁样行为,其机制可能与抑制小胶质细胞TLR4/NF-κB通路,进而下调炎症因子的表达有关。

关键词: 抑郁症, 加味逍遥散, LPS, 小胶质细胞, TLR4/NF-κB, 大鼠

Abstract: Objective: To investigate the effects of modified Xiaoyao San on TLR4/NF-κB pathway in hippocampal microglia of LPS-induced depression model rats, and to explore its antidepressant mechanism. Methods: SD rats were randomly divided into control, model, fluoxetine (10 mg·kg-1), low and high dose of modified Xiaoyao San (3.64, 7.28g·kg-1) group. The depression model was established by chronic LPS injection (ip, 0.5 mg·kg-1) and rats were treated by intragastric administration for 14 days. After the model was established, the depression-like behavior of rats was evaluated by open field and forced swimming test. The expression of microglia marker protein Iba-1 was detected by immunohistochemistry. The levels of TNF-α and IL-6 in hippocampal homogenate were detected by ELISA method and the expressions of TLR4 and NF-κB protein in hippocampus were detected by Western blot. Results: Compared with control group, the depression-like behavior was significant in model group rats (P<0.01), the microglia in the brain was activated (P<0.01), the contents of TNF-α and IL-6 in the hippocampus were increased (P<0.01), and the expression levels of TLR4 and NF-κB proteins were up-regulated (P<0.01). Compared with model group, the depression-like behavior of the rats in the fluoxetine and high-dose modified Xiaoyao San group was significantly alleviated (P<0.05), the expression of Iba-1 in microglia returned to normal (P<0.01), the contents of TNF-α and IL-6 were decreased (P<0.01), and the expression levels of TLR4 and NF-κB protein were decreased (P<0.05). Compared with fluoxetine group, the high-dose modified Xiaoyao San group had no statistically significant difference in each index, suggesting that there was no significant difference in the antidepressant effect between the two groups. Conclusion: Modified Xiaoyao San can significantly improve the depression-like behavior in rats, and its mechanism may be related to inhibiting the TLR4/NF-κB pathway of microglia and down-regulating the expression of inflammatory factors.

Key words: depression, modified Xiaoyao San, LPS, microglia, TLR4/NF-κB, rat

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