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CJAP ›› 2020, Vol. 36 ›› Issue (4): 354-357.doi: 10.12047/j.cjap.5936.2020.076

• ORIGINAL ARTICLES • Previous Articles     Next Articles

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

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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