目的: 探索复合地龙合剂（compound Dilong agentia,DCA）对抑郁症（major depressive disorder,MDD）小鼠的影响。方法: 采用慢性不可预测应激模型法（chronic unpredictable mild stress,CUMS）法构建MDD模型。小鼠分为control组、MDD组、MDD+paroxetine组、MDD+DCA组。采用强迫游泳实验、悬尾实验、糖水偏好实验评估小鼠抑郁样行为;HE染色检测小鼠海马CA1区神经元病理变化;免疫组化检查海马NF-κB的表达;WB检测海马BDNF表达;ELISA法检测TNF-α、IL-1β和IL-6水平。结果: MDD+DCA组小鼠体重显著高于MDD组。MDD+DCA组小鼠糖水偏好率显著高于MDD组。强迫游泳实验和悬尾实验结果均显示,MDD+DCA组小鼠不动时间显著短于MDD组。HE染色和免疫组化结果显示,DCA可显著减轻CUMS法诱导的MDD小鼠海马CA1神经元病理改变,降低NF-κB的表达。MDD+DCA组小鼠BDNF蛋白表达显著高于MDD组。MDD+DCA组小鼠脑组织中TNF-α、IL-1β和IL-6表达显著低于MDD组。结论: 复合地龙合剂能降低MDD模型小鼠脑组织炎症反应,提高其海马组织中BDNF表达,促进神经修复,显著改善抑郁样行为。
Abstract
Objective To explore the effects of Dilong Composite Agentia (DCA) on mice with major depressive disorder (MDD). Methods The classical method-chronic unpredictable mild stress (CUMS) was used to construct MDD model. In the experiment, mice were evenly divided into control group, MDD group, MDD+ Paroxetine group and MDD + DCA group. We used the following techniques to indicate the results: sugar water preference experiments, tail suspension experiments, and forced swimming experiments for behavioral testing; HE staining to examine the pathological alterations in the hippocampal CA1 neurons of the mice; Immunohistochemical staining techniques to examine the expression of NF-κB in hippocampus. Using WB to detect the BDNF expression in hippocampal tissue and Elisa to detect the expression of TNF - α, IL-1β, and IL-6 in mouse brain tissue. Results The body weight of mice in the MDD+DCA group was apparently higher than that in the MDD group. The glucose preference rate of mice in the MDD+DCA group was significantly higher than that in the MDD group. The results of forced swimming and tail suspension experiments all showed that the stationary time of mice in the MDD+DCA group was significantly shorter than that in the MDD group. HE staining and immunohistochemical staining demonstrated that DCA significantly mitigated the pathological alterations in CA1 neurons of MDD mice induced by chronic unpredictable mild stress, along with a decrease in the expression of NF-κB. The expression of brain-derived neurotrophic factor (BDNF) protein of MDD+DCA group mice were obviously higher than that in the MDD group. The levels of TNF - α, IL-1 β, and IL-6 in the brain tissue of mice in the MDD+DCA group were apparently lower than in the MDD group. Conclusion Therefore, we conclude that DCA promotes neural repair and significantly improves depression behaviors through such mechanisms, which we propose with experimental evidence, that DCA increases BDNF expression in the hippocampal tissue and further reduces inflammation in the brain tissue of mice with depression.
关键词
中药合剂 /
地龙 /
抑郁症 /
炎症因子 /
神经营养因子
Key words
traditional chinese medicine composites /
Dilong /
major depressive disorder /
inflammatory factors /
neurotrophic factors
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] 李青栋, 许晶. 抑郁症的概念及分类研究历史[J]. 医学与哲学, 2009, 30(11): 78-80
[2] COVID-19 Mental Disorders Collaborators. Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic[J]. Lancet, 2021, 398(10312): 1700-1712.
[3] 荆桧, 潘夏彦, 张彬. 卒中后抑郁中医药辨治思路浅析[J]. 中医临床研究, 2022, 14(35): 93-96.
[4] RUBERTO L V, JHA K M, MURROUGH W J.Pharmacological treatments for patients with treatment-resistant depression[J]. Pharmaceuticals, 2020, 13(6): 116.
[5] 王春芳, 田文国, 陈金鹏, 等. 中药抗抑郁作用及其机制研究进展[J]. 中草药, 2022, 53(9): 2890-2901.
[6] 王惠芹, 王真真, 林美妤, 等. 抑郁症发病与神经营养因子异常研究进展[J]. 中国药理学通报, 2020, 36(10): 1333-1337.
[7] LUO H, XIANG Y, QU X, et al.Apelin-13 Suppresses Neuroinflammation Against Cognitive Deficit in a Streptozotocin-Induced Rat Model of Alzheimer's Disease Through Activation of BDNF-TrkB Signaling Pathway[J]. Front Pharmacol, 2019, 10: 395.
[8] LUO H, HAN L, XU J.Apelin/APJ system: A novel promising target for neurodegenerative diseases[J]. J Cell Physiol, 2020, 235(2): 638-657.
[9] 傅炜昕, 李建华, 董占双, 等. 免疫活性地龙肽的制备及其对小鼠巨噬细胞活性的影响[J]. 微生物学杂志, 2008, 28(1): 36-40.
[10] 李煜, 李永娟, 刘峰, 等. MIS-TLIF术后辅助通督活血汤治疗腰椎间盘突出症的临床疗效观察[J]. 中国实用医药, 2022, 17(10): 151-153.
[11] 李春丰. 黄芩-石菖蒲药对对抑郁症模型小鼠学习记忆行为及海马区TLR4、NF-κB及5-HT表达的影响[D]. 唐山:华北理工大学,2023.
[12] 张阔, 杨静玉, 吴春福. 抑郁症的病理生理学基础及动物模型研究进展[J]. 神经药理学报, 2017, 7(4): 8-16.
[13] 闫惠淳, 王通宇, 温歌华, 等. 抑郁症动物模型的研究进展[J]. 解剖科学进展, 2018, 24 (3): 326-329+333.
[14] 高贵元, 黄捷, 刘丹, 等. 抑郁症的发病机制及抗抑郁药物的研究进展[J]. 中国医药导报, 2021, 18 (1): 52-55+70.
[15] 王婷婷, 吴辉, 张蓓蓓, 等. 抑郁症发病机制与临床抗抑郁药研究进展[J]. 生命科学仪器, 2014, 12(6): 28-33.
[16] 苗茸茸, 曲显俊. 抑郁症动物模型的研究进展[J]. 实验动物科学, 2019, 36(3): 80-85.
[17] 王琳, 张兴军, 金黎明, 等. 抗抑郁药物的研究进展[J]. 化学世界, 2022, 63(2): 83-93.
[18] 张克艺. 加味桂枝加龙骨牡蛎汤治疗抑郁症心阳虚证临床疗效观察[D]. 太原: 山西中医药大学, 2021.
[19] 杨丽英, 王艳丽, 郝立炜. 中医药治疗抑郁症的研究进展[J]. 中医药信息, 2022, 39(7): 86-89.
[20] 吴志鹏, 王永盛, 王苹莉, 等. 活血解郁汤结合氟西汀对卒中后抑郁血清脑源性神经营养因子的影响[J]. 中华中医药学刊, 2021, 39(2): 185-188.
[21] 王丹, 邱长云, 孟凡涛, 等. 慢性不可预知应激所致抑郁小鼠性行为受损及VTA脑区BDNF的表达下降[J]. 安徽医科大学学报, 2022, 57(3): 455-460.
[22] COOPER EL, HIRABAYASHI K, BALAMURUGAN M.Dilong: food for thought and medicine[J]. J Tradit Complement Med, 2012, 2(4): 242-248.
[23] PURGATO M, PAPOLA D, GASTALDON C, et al. Paroxetine versus other anti-depressive agents for depression[J]. Cochrane Database Syst Rev, 2014, 2014 (4): CD006531.
[24] WILDE MI, WHITTINGTON R.PAROXETINE. A pharmacoeconomic evaluation of its use in depression[J]. Pharmacoeconomics, 1995, 8(1): 62-81.
基金
国家级大学生创新创业训练计划项目“复合地龙剂对小鼠抑郁症的影响及其机制研究” [教高司函（2022）10号-202210823004]
PDF(3775 KB)
