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

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.