【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。更多还原

【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( 3.64,7.28 g·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.更多还原