[加味逍遥散对脂多糖诱导抑郁模型大鼠海马小胶质细胞TLR4/NF-κB通路的影响]

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

作者信息

Guo Rui, Qin Wei-Shuai, Zhang Shuang-Yong, Zhang Shu-Ling

机构信息

Department of Encephalopathy, Zhengzhou Chinese Medicine Hospital, Zhengzhou 450007.

Department of Neurology, Zhengzhou People 's Hospital, Zhengzhou 450003, China.

出版信息

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2020 Jul;36(4):354-357. doi: 10.12047/j.cjap.5936.2020.076.

DOI:10.12047/j.cjap.5936.2020.076

PMID:33167098

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), low and high dose of modified Xiaoyao San (3.64, 7.28g·kg) group. The depression model was established by chronic LPS injection (, 0.5 mg·kg) 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 (＜0.01), the microglia in the brain was activated (＜0.01), the contents of TNF-α and IL-6 in the hippocampus were increased (＜0.01), and the expression levels of TLR4 and NF-κB proteins were up-regulated (＜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 (＜0.05), the expression of Iba-1 in microglia returned to normal (＜0.01), the contents of TNF-α and IL-6 were decreased (＜0.01), and the expression levels of TLR4 and NF-κB protein were decreased (＜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.

摘要

目的

探讨加味逍遥散对脂多糖诱导的抑郁模型大鼠海马小胶质细胞TLR4/NF-κB通路的影响，以探究其抗抑郁机制。

方法

将SD大鼠随机分为对照组、模型组、氟西汀（10 mg·kg）组、加味逍遥散低剂量（3.64 g·kg）组和高剂量（7.28 g·kg）组。通过慢性注射脂多糖（0.5 mg·kg）建立抑郁模型，大鼠灌胃给药14天。造模后，通过旷场试验和强迫游泳试验评估大鼠的抑郁样行为。采用免疫组织化学法检测小胶质细胞标志物蛋白Iba-1的表达。采用ELISA法检测海马匀浆中TNF-α和IL-6的水平，采用Western blot法检测海马中TLR4和NF-κB蛋白的表达。

结果

与对照组相比，模型组大鼠抑郁样行为明显（P＜0.01），脑内小胶质细胞激活（P＜0.01），海马中TNF-α和IL-6含量增加（P＜0.01），TLR4和NF-κB蛋白表达水平上调（P＜0.01）。与模型组相比，氟西汀组和加味逍遥散高剂量组大鼠抑郁样行为明显减轻（P＜0.05），小胶质细胞中Iba-1表达恢复正常（P＜0.01），TNF-α和IL-6含量降低（P＜0.01），TLR4和NF-κB蛋白表达水平降低（P＜0.05）。与氟西汀组相比，加味逍遥散高剂量组各指标差异无统计学意义，提示两组抗抑郁效果无明显差异。