逍遥散对脂多糖诱导抑郁样行为的影响
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摘要
目的探讨逍遥散对脂多糖诱导抑郁样行为的影响。方法脂多糖诱导抑郁样小鼠模型,小鼠随机分为空白组、模型组、氟西汀组(3.03 mg/kg)及逍遥散低、高剂量组(15、30 g/kg),检测强迫游泳实验、悬尾实验中不动时间,血清、海马、皮层IL-6、TNF-α水平,海马、皮层IDO、5-HT水平,尼氏染色观察海马神经元形态学变化。然后,脂多糖诱导大鼠海马神经元细胞炎症模型,细胞随机分为空白组、模型组、氟西汀组(10μmol/L)及空白血清、含药血清低、高剂量组(4%、8%),检测上清液NO、IL-6、TNF-α水平,裂解液5-HT、IDO水平,IL-6、TNF-α、5-HT1A、IDO1 mRNA表达。结果与模型组比较,逍遥散组显著缩短强迫游泳实验中不动时间(P<0.01),显著降低血清IL-6水平及皮层IL-6、TNF-α、IDO水平(P<0.05,P<0.01),显著升高海马5-HT水平(P<0.01);高剂量组显著缩短悬尾实验中不动时间(P<0.01),显著上调皮层5-HT水平(P<0.01),显著增加海马平均光密度(P<0.05);低剂量组显著降低海马IL-6水平(P<0.05)。与模型组比较,含药血清组显著下调IL-6、TNF-α、IDO1 mRNA表达(P<0.05,P<0.01),显著上调5-HT1A mRNA表达(P<0.01);高剂量组显著下调NO、IL-6、TNF-α、IDO水平(P<0.01),显著上调5-HT水平(P<0.01);低剂量组显著降低IDO水平(P<0.01)。结论逍遥散对脂多糖诱导抑郁样行为有拮抗作用,其机制可能与抑制炎症反应有关。
AIM To explore the effects of Xiaoyao Powder on lipopolysaccharide-induced depressive-like behaviors.METHODS The mouse model for depressive-like behaviors was induced by lipopolysaccharide, mice were randomly divided into blank group, model group, fluoxetine group(3.03 mg/kg) and Xiaoyao Powder low-dose, high-dose groups(15, 30 g/kg), immobility time in forced swim test and tail suspension test, IL-6, TNF-α levels in serum, hippocampus and cortex, IDO, 5-HT levels in hippocampus and cortex were detected, and Nissl staining was applied to observing the morphological changes of hippocampal neurons. Subsequently, the rat model for hippocampal neuron cell inflammatory was induced by lipopolysaccharide, cells were randomly divided into blank group, model group, fluoxetine group(10 μmol/L) and blank serum, medicated serum low-dose, high-dose groups(4%, 8%), NO, IL-6,TNF-α levels in supernatant, 5-HT, IDO levels in lysate, IL-6, TNF-α, 5-HT, IDO mRNA expressions were detected.RESULTS Compared with the model group, the Xiaoyao Powder groups demonstrated significantly shortened immobility time in forced swim test(P<0.01), markedly decreased IL-6 level in serum and IL-6, TNF-α, IDO levels in cortex(P<0.05, P<0.01), obviously increased 5-HT level in hippocampus(P<0.01), among which the high-dose group exhibited significantly shortened immobility time in tail suspension test(P<0.01), markedly up-regulated 5-HT level in cortex(P<0.01), obviously increased mean optical density in hippocampus(P<0.05), and the low-dose group showed significantly decreased IL-6 level in hippocampus(P<0.05). Compared with the model group, the medicated serum groups demonstrated significantly down-regulated IL-6, TNF-α, IDO1 mRNA expressions(P<0.05, P<0.01), markedly up-regulated 5-HT1 A mRNA expression(P<0.01), the high-dose group exhibited significantly down-regulated NO, IL-6, TNF-α, IDO levels(P<0.01), markedly up-regulated 5-HT level(P<0.01), and the low-dose group showed significantly decreased IDO level(P<0.01).CONCLUSION Xiaoyao Powder reveals its antagonistic effects on lipopolysaccharide-induced depressive-like behaviors, whose mechanism may contribute to the inhibition of inflammatory reactions.
AIM To explore the effects of Xiaoyao Powder on lipopolysaccharide-induced depressive-like behaviors.METHODS The mouse model for depressive-like behaviors was induced by lipopolysaccharide, mice were randomly divided into blank group, model group, fluoxetine group(3.03 mg/kg) and Xiaoyao Powder low-dose, high-dose groups(15, 30 g/kg), immobility time in forced swim test and tail suspension test, IL-6, TNF-α levels in serum, hippocampus and cortex, IDO, 5-HT levels in hippocampus and cortex were detected, and Nissl staining was applied to observing the morphological changes of hippocampal neurons. Subsequently, the rat model for hippocampal neuron cell inflammatory was induced by lipopolysaccharide, cells were randomly divided into blank group, model group, fluoxetine group(10 μmol/L) and blank serum, medicated serum low-dose, high-dose groups(4%, 8%), NO, IL-6,TNF-α levels in supernatant, 5-HT, IDO levels in lysate, IL-6, TNF-α, 5-HT, IDO mRNA expressions were detected.RESULTS Compared with the model group, the Xiaoyao Powder groups demonstrated significantly shortened immobility time in forced swim test(P<0.01), markedly decreased IL-6 level in serum and IL-6, TNF-α, IDO levels in cortex(P<0.05, P<0.01), obviously increased 5-HT level in hippocampus(P<0.01), among which the high-dose group exhibited significantly shortened immobility time in tail suspension test(P<0.01), markedly up-regulated 5-HT level in cortex(P<0.01), obviously increased mean optical density in hippocampus(P<0.05), and the low-dose group showed significantly decreased IL-6 level in hippocampus(P<0.05). Compared with the model group, the medicated serum groups demonstrated significantly down-regulated IL-6, TNF-α, IDO1 mRNA expressions(P<0.05, P<0.01), markedly up-regulated 5-HT1 A mRNA expression(P<0.01), the high-dose group exhibited significantly down-regulated NO, IL-6, TNF-α, IDO levels(P<0.01), markedly up-regulated 5-HT level(P<0.01), and the low-dose group showed significantly decreased IDO level(P<0.01).CONCLUSION Xiaoyao Powder reveals its antagonistic effects on lipopolysaccharide-induced depressive-like behaviors, whose mechanism may contribute to the inhibition of inflammatory reactions.
引文
[1] 段富津. 方剂学[M]. 上海:上海科学技术出版社, 1995.
[2] 李云,苟小军,周明眉,等.复方丹参滴丸对 LPS 造抑郁样行为模型小鼠的抗抑郁作用实验研究[J].上海中医药杂志,2016,50(3):83-86.
[3] 周桢昊. 逍遥散及其组方抗抑郁作用及机制研究——对大鼠海马神经元的保护及BDNF、TrkB表达的影响[D]. 成都:成都中医药大学,2007.
[4] Piser T M. Linking the cytokine and neurocircuitry hypotheses of depression: a translational framework for discovery and development of novel anti-depressants[J]. Brain Behav Immun, 2010, 24(4):515-524.
[5] Aalling N, Hageman I, Miskowiak K, et al. Erythropoietin prevents the effect of chronic restraint stress on the number of hippocampal CA3c dendritic terminals—relation to expression of genes involved in synaptic plasticity, angiogenesis, inflammation, and oxidative stress in male rats[J]. J Neurosci Res, 2017, 96(1): 103-116.
[6] Brooks A K, Janda T M, Lawson M A, et al. Desipramine decreases expression of human and murine indoleamine-2,3-dioxygenases[J]. Brain Behav Immun, 2017, 62: 219-229.
[7] Parrott J M, Redus L, O’Connor J C. Kynurenine metabolic balance is disrupted in the hippocampus following peripheral lipopolysaccharide challenge[J]. J Neuroinflamm,2016, 13:124.
[8] Souza L C, Jesse C R, de Gomes M G, et al. Intracerebroventricular administration of streptozotocin as an experimental approach to depression: evidence for the involvement of proinflammatory cytokines and indoleamine-2,3-dioxygenase[J]. Neurotox Res, 2017, 31(4):464-477.
[9] Corona A W, Norden D M, Skendelas J P, et al. Indoleamine 2,3-dioxygenase inhibition attenuates lipopolysaccharide induced persistent microglial activation and depressive-like complications in fractalkine receptor (CX3CR1)-deficient mice[J]. Brain Behav Immun, 2013, 31:134-142.
[10] Guan X T, Shao F, Xie X, et al. Effects of aspirin on immobile behavior and endocrine and immune changes in the forced swimming test: comparison to fluoxetine and imipramine[J]. Pharmacol Biochem Behav, 2014, 124:361-366.
[11] 彭成. 中药药理学[M]. 北京:中国中医药出版社,2012:96.
[12] Han N R, Kim H M, Jeong H J. Inactivation of cystein-aspartic acid protease (caspase)-1 by saikosaponin A[J]. Biol Pharm Bull, 2011, 34(6):817-823.
[13] 张旭,赵芬琴. 生姜提取液抗炎镇痛作用研究[J]. 河南大学学报(医学版),2015,34(1):26-28.
[14] Cheng H M, Hsiang C Y, Chen G W, et al. Inhibition of lipopolysaccharide-induced interleukin-1β and tumor necrosis factor-α production by menthone through nuclear factor-κB signaling pathway in HaCat cells[J]. Chin J Physiol, 2008, 51(3):160-166.
[15] 李晓红,齐云,蔡润兰,等.甘草总皂苷抗炎作用机制研究[J].中国实验方剂学杂志,2010,16(5):110-113.
[2] 李云,苟小军,周明眉,等.复方丹参滴丸对 LPS 造抑郁样行为模型小鼠的抗抑郁作用实验研究[J].上海中医药杂志,2016,50(3):83-86.
[3] 周桢昊. 逍遥散及其组方抗抑郁作用及机制研究——对大鼠海马神经元的保护及BDNF、TrkB表达的影响[D]. 成都:成都中医药大学,2007.
[4] Piser T M. Linking the cytokine and neurocircuitry hypotheses of depression: a translational framework for discovery and development of novel anti-depressants[J]. Brain Behav Immun, 2010, 24(4):515-524.
[5] Aalling N, Hageman I, Miskowiak K, et al. Erythropoietin prevents the effect of chronic restraint stress on the number of hippocampal CA3c dendritic terminals—relation to expression of genes involved in synaptic plasticity, angiogenesis, inflammation, and oxidative stress in male rats[J]. J Neurosci Res, 2017, 96(1): 103-116.
[6] Brooks A K, Janda T M, Lawson M A, et al. Desipramine decreases expression of human and murine indoleamine-2,3-dioxygenases[J]. Brain Behav Immun, 2017, 62: 219-229.
[7] Parrott J M, Redus L, O’Connor J C. Kynurenine metabolic balance is disrupted in the hippocampus following peripheral lipopolysaccharide challenge[J]. J Neuroinflamm,2016, 13:124.
[8] Souza L C, Jesse C R, de Gomes M G, et al. Intracerebroventricular administration of streptozotocin as an experimental approach to depression: evidence for the involvement of proinflammatory cytokines and indoleamine-2,3-dioxygenase[J]. Neurotox Res, 2017, 31(4):464-477.
[9] Corona A W, Norden D M, Skendelas J P, et al. Indoleamine 2,3-dioxygenase inhibition attenuates lipopolysaccharide induced persistent microglial activation and depressive-like complications in fractalkine receptor (CX3CR1)-deficient mice[J]. Brain Behav Immun, 2013, 31:134-142.
[10] Guan X T, Shao F, Xie X, et al. Effects of aspirin on immobile behavior and endocrine and immune changes in the forced swimming test: comparison to fluoxetine and imipramine[J]. Pharmacol Biochem Behav, 2014, 124:361-366.
[11] 彭成. 中药药理学[M]. 北京:中国中医药出版社,2012:96.
[12] Han N R, Kim H M, Jeong H J. Inactivation of cystein-aspartic acid protease (caspase)-1 by saikosaponin A[J]. Biol Pharm Bull, 2011, 34(6):817-823.
[13] 张旭,赵芬琴. 生姜提取液抗炎镇痛作用研究[J]. 河南大学学报(医学版),2015,34(1):26-28.
[14] Cheng H M, Hsiang C Y, Chen G W, et al. Inhibition of lipopolysaccharide-induced interleukin-1β and tumor necrosis factor-α production by menthone through nuclear factor-κB signaling pathway in HaCat cells[J]. Chin J Physiol, 2008, 51(3):160-166.
[15] 李晓红,齐云,蔡润兰,等.甘草总皂苷抗炎作用机制研究[J].中国实验方剂学杂志,2010,16(5):110-113.