加味柴胡加龙骨牡蛎汤治疗卒中后抑郁模型大鼠疗效及对突触可塑性的影响OA
Exploring the Effects of Modified Chaihu Plus Longgu Muli Decoction Improving Synaptic Plasticity in a Rat Model of Post-Stroke Depression
目的:观察加味柴胡加龙骨牡蛎汤对卒中后抑郁(PSD)模型大鼠疗效及对突触可塑性的影响,探讨加味柴胡加龙骨牡蛎汤治疗PSD的作用机制.方法:将50只雄性SD大鼠随机分为假手术组、脑梗(MCAO)组、PSD组、阳性对照组(盐酸氟西汀1.58mg·kg-1)和中药组(加味柴胡加龙骨牡蛎汤11.7g·kg-1),每组10只.采用大脑中动脉栓塞梗死方法构建脑梗死模型,在此模型基础上施加慢性不可预见应激(CUMS)干预及孤养法,成功制备PSD模型后连续灌胃给药3周.通过旷场实验反映大鼠抑郁相关行为,尼氏染色检测大鼠海马CA1区神经元数量,免疫组化检测大鼠海马CA1区突触后致密蛋白-95(PSD95)、突触素(SYN)蛋白表达情况,免疫印迹法检测大鼠海马组织脑源性神经营养因子(BDNF)、血管内皮生长因子 A(VEGFA)蛋白表达水平.结果:旷场实验结果显示,PSD组大鼠在中心区域停留时间和中心活动距离明显低于假手术组及 MCAO组(P<0.05),中药组和阳性对照组大鼠中心区域停留时间、中心区域活动距离均明显高于PSD组[中心区停留时间中药组较PSD组延长378%(MD=17.23s,95%CI 12.4-22.1),活动距离增加261%(MD=2.09m,95%CI 1.74-2.44)](P<0.05).尼氏染色结果显示,MCAO组和PSD组神经元数目明显少于假手术组(P<0.05),阳性对照组和中药组神经元数目明显多于 MCAO组和PSD组(P<0.05).免疫组化检测结果显示,MCAO组和PSD组SYN、PSD95表达明显低于假手术组(P<0.05),阳性对照组SYN表达明显高于 MCAO组和PSD组(P<0.05),中药组SYN、PSD95表达明显高于 MCAO组和PSD组(P<0.05).免疫印迹法检测结果显示,MCAO组和PSD组BDNF、VEGFA蛋白表达量明显低于假手术组(P<0.05),阳性对照组和中药组BDNF、VEGFA蛋白表达量均明显高于 MCAO组和PSD组(P<0.05).结论:加味柴胡加龙骨牡蛎汤可通过改善突触微环境、提高突触可塑性来减少PSD大鼠海马神经元缺失,进而改善其抑郁相关行为.
Objective:To observe the therapeutic effect of Modified Chaihu Plus Longgu Muli Decoction on PSD model rats and its impact on synaptic plasticity,and to explore the mechanism of this formula in treating PSD.Methods:Fifty male SD rats were randomly allocated to five groups(n=10 each):sham-operated group,middle cerebral artery occlu-sion(MCAO)group,PSD group,positive control group(fluoxetine hydrochloride 1.58 mg·kg-1),and traditional Chi-nese medicine group(Modified Chaihu Plus Longgu Muli Decoction 11.7 g·kg-1).Cerebral infarction models were es-tablished using middle cerebral artery occlusion,and PSD models were successfully prepared by applying chronic un-predictable mild stress(CUMS)and solitary housing based on this model.After successful modeling,drugs were ad-ministered by gavage for 3 consecutive weeks.Depressive-like behaviors were assessed using the open field test,neuro-nal counts in the hippocampal CA1 region were detected by Nissl staining,PSD95 and SYN protein expression in the hippocampal CA1 region was examined via immunohistochemistry,and BDNF and VEGFA protein levels in hippocam-pal tissues were measured by Western blot.Results:Open field test results showed that central zone duration and movement distance in the PSD group were significantly lower than those in the sham-operated and MCAO groups(P<0.05),while both the traditional Chinese medicine(TCM)and positive control groups exhibited significantly higher values than the PSD group(The duration of center zone activity in the Chinese materia medica group was prolonged by 378%(MD=17.23 s,95%CI:12.4-22.1)compared with the PSD group;the movement distance was increased by 261%(MD=2.09 m,95%CI:1.74-2.44))(P<0.05).Nissl staining revealed significantly fewer neurons in the MCAO and PSD groups compared to the sham-operated group(P<0.05),with higher neuronal counts in the positive control and Chinese materia medica groups versus the MCAO and PSD groups(P<0.05).Immunohistochemistry in-dicated lower SYN and PSD95 expression in the MCAO and PSD groups than in the sham-operated group(P<0.05).The positive control group showed higher SYN expression than the MCAO and PSD groups(P<0.05),while the Chi-nese materia medica group demonstrated elevated expression of both SYN and PSD95 compared to the MCAO and PSD groups(P<0.05).Western blot analysis showed reduced BDNF and VEGFA protein expression in the MCAO and PSD groups relative to the sham-operated group(P<0.05),whereas the positive control and Chinese materia medica groups exhibited increased expression of these proteins compared to the disease model groups(P<0.05).Conclusion:Modified Chaihu Plus Longgu Muli Decoction improves synaptic microenvironment and enhances synaptic plasticity,thereby reducing hippocampal neuronal loss and ameliorating depressive behaviors in PSD rats.
昝树杰;覃姻姻;覃芳艳;覃启京;周欣梅;梁明坤;覃辉
天津中医药大学第一附属医院,天津 300193广西中医药大学,广西 南宁 530000广西中医药大学附属国际壮医医院,广西 南宁 530000广西中医药大学附属国际壮医医院,广西 南宁 530000广西中医药大学附属瑞康医院,广西 南宁 530000广西中医药大学附属瑞康医院,广西 南宁 530000广西中医药大学附属国际壮医医院,广西 南宁 530000
医药卫生
加味柴胡加龙骨牡蛎汤卒中后抑郁中药突触可塑性突触微环境
Modified Chaihu Plus Longgu Muli Decoctionpost-stroke depressionChinese materia medicasynaptic plasticitysynaptic microenvironment
《亚太传统医药》 2026 (5)
15-21,7
广西高校中青年科研基础能力提升项目(2020KY07010)广西中医药大学博士科研启动项目(XP020090)广西国际壮医医院引进人才科研启动基金项目(GZ2023RC005)
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