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*

doi:10.12047/j.cjap.5936.2020.076

摘要/Abstract

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

中图分类号:

R277.7

郭锐, 秦卫帅, 张双勇, 张淑玲. 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^*[J]. 中国应用生理学杂志, 2020, 36(4): 354-357.

GUO Rui, QIN Wei-shuai, ZHANG Shuang-yong, ZHANG Shu-ling. Effects of modified Xiaoyao San on TLR4/NF-κB pathway in hippocampal microglia of LPS-induced depression model rats[J]. CJAP, 2020, 36(4): 354-357.

参考文献

[1] Bode K, Vogel R, Walker J. Health care costs of borderline personality disorder and matched controls with major depressive disorder: a comparative study based on anonymized claimsdata[J]. Eur J Health Econ, 2017, 18(9): 1125-1135.
[2] Maes M, Anderson G, Kubera M. Targeting classical IL-6 signalling or IL-6 trans-signalling in depression[J] ? Expert Opin Ther Targets, 2014, 18(5): 495-512.
[3] Jiang M, Qin P, Yang X. Comorbidity between depression and asthma via immune-inflammatory pathways: a meta-analysis[J]. J Affect Disord, 2014, 166: 22-29.
[4] Brites D, Fernandes A. Neuroinflammation and depression: Microglia activation, extracellular microvesicles and microRNA dysregulation[J]. Front Cell Neurosci, 2015, 17(9): 476-481.
[5] 周杰. 加味逍遥胶囊治疗轻中度抑郁症气郁化火证多中心随机对照临床研究[D]. 北京: 中国中医科学院.
[6] Wang Y, Cui XL, Liu YF, et al. LPS inhibits the effects of fluoxetine on depression-like behavior and hippocampal neurogenesis in rats[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2011, 35(8): 1831-1835.
[7] Gong Y, Tong L, Yang R, et al. Dynamic changes in hippocampal microglia contribute to depressive-like behavior induced by early social isolation[J]. Neuropharmacology, 2018, 135: 223-233.
[8] Steiner J, Walter M, Gos T, et al. Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: evidence for an immune-modulated glutamatergic neurotransmission[J] ? J Neuroinflamm, 2011, 8: 94-102.
[9] Darsalia V, Hua SS, Larsson M, et al. Exendin-4 reduces ischemic brain injury in normal and aged type 2 diabetic mice and promotes microglial M2 polarization[J]. PLoS One, 2014, 9(8): 1-7.
[10] Zuo WQ, Hu YJ, Yang Y, et al. Sensitivity of spiral ganglion neurons to damage caused by mobile phone electromagnetic radiation will increase in lipopolysaccharide-induced inflammation in vitro model[J]. J Neuroinflammation, 2015, 29(12): 105-110.
[11] Wang C, Sun H, Song Y, et al. Pterostilbene attenuates inflammation in rat heart subjected to ischemia-reperfusion: role of TLR4/NF-κB signaling pathway[J]. Int J Clin Exp Med, 2015, 8(2): 1737-1746.
[12] 蒋伟, 张弦, 周爱玲. TLR4/P38/JNK信号通路在海马神经元凋亡中的作用[J].中国应用生理学杂志, 2016, 32(6): 571-576.
[13] Brancato SK, Thomay AA, Daley JM, et al. Toll-like receptor 4 signaling regulates the acute local inflammatory response to injury and the fibrosis/neovascularization of sterile wounds[J]. Wound Repair Regen, 2013, 21(4): 624-633.
[14] Wang SL, Duan L, Xia B, et al. Dexmedetomidine preconditioning plays a neuroprotective role and suppresses TLR4/NF-κB pathways model of cerebral ischemia reperfusion[J]. Biomed Pharmacother, 2017, 93(9): 1337-1342.
[15] 于林, 吴升伟, 禤正正, 等. 加味逍遥散对胃肠功能失调的抑郁大鼠脑肠肽SS、GAS表达的影响[J]. 时珍国医国药, 2017, 28(6): 1290-1292.
[16] 温世春. 加味逍遥散近代临床应用进展[J]. 中国民间疗法, 2019, 27(18): 108-109.

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^*

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

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