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基于BDNF/CREB信号通路探讨藏药十一味维命胶囊的抗抑郁作用机制
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作者 李鑫 王琼莹 +6 位作者 马召田 于雪 孙洪昊 仁青东主 久美彭措 东知加 任小巧 《云南中医中药杂志》 2024年第8期61-67,共7页
目的基于BDNF/CREB信号通路对藏药十一味维命胶囊对抑郁症小鼠的抗抑郁作用及机制进行研究。方法将48只小鼠随机分为正常组(n=12)、造模组(n=36),造模组采用CUMS结合CRS方法造模3周。成模后,将造模组小鼠随机分为模型组、十一味维命胶囊... 目的基于BDNF/CREB信号通路对藏药十一味维命胶囊对抑郁症小鼠的抗抑郁作用及机制进行研究。方法将48只小鼠随机分为正常组(n=12)、造模组(n=36),造模组采用CUMS结合CRS方法造模3周。成模后,将造模组小鼠随机分为模型组、十一味维命胶囊组(藏药组)、氟西汀组,各12只,干预4周。采用行为学实验对抑郁症小鼠模型进行评估。WB法检测小鼠海马BDNF、GDNF、NGF、p-CREB/CREB、PSD-95表达;IHC法检测小鼠海马BDNF、GDNF、p-CREB MOD值。结果造模3周后,造模组小鼠出现抑郁样行为,小鼠体质量、糖水偏好率均低于正常组(P<0.01);不动时间长于正常组(P<0.01);给药4周后,模型组小鼠体质量、糖水偏好率低于正常组(P<0.01);不动时间长于正常组(P<0.01);藏药组、氟西汀组小鼠体质量、糖水偏好率均高于模型组(P<0.05或P<0.01);不动时间均短于模型组(P<0.01)。模型组小鼠海马BDNF、GDNF、PSD-95蛋白表达及BDNF、GDNF、p-CREB MOD值均低于正常组(P<0.05或P<0.01)。藏药组、氟西汀组小鼠海马BDNF、GDNF、p-CREB/CREB、PSD-95蛋白表达均高于模型组(P<0.05或P<0.01)。藏药组小鼠BDNF、GDNF MOD值均高于模型组(P<0.05或P<0.01);氟西汀组小鼠海马BDNF、GDNF、p-CREB MOD值均高于模型组(P<0.01)。结论十一味维命胶囊可以改善抑郁症小鼠的抑郁行为,其作用机制可能与调控BDNF/CREB信号通路有关。 展开更多
关键词 抑郁症 十一味维命胶囊 BDNF/CREB信号通路 小鼠
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CUMS结合CRS对抑郁症小鼠海马神经胶质细胞及突触可塑性的影响
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作者 李鑫 王琼莹 +3 位作者 马召田 孙洪昊 于雪 任小巧 《海南医学院学报》 CAS 2023年第2期87-95,共9页
目的:探讨CUMS结合CRS对小鼠海马神经胶质细胞及突触可塑性相关蛋白的影响。方法:将40只小鼠随机分为正常组(n=20)、模型组(n=20)。模型组采用CUMS结合CRS的方法制备抑郁症小鼠模型,持续造模7周。采用糖水偏好实验、旷场实验及悬尾实验... 目的:探讨CUMS结合CRS对小鼠海马神经胶质细胞及突触可塑性相关蛋白的影响。方法:将40只小鼠随机分为正常组(n=20)、模型组(n=20)。模型组采用CUMS结合CRS的方法制备抑郁症小鼠模型,持续造模7周。采用糖水偏好实验、旷场实验及悬尾实验对造模3周、7周末小鼠进行行为学评估;实验结束后取材,酶联免疫吸附法检测小鼠海马TNF-a的含量;免疫组化法检测小鼠海马CA1区、CA3区、DG区Iba-1、GFAP MOD值;蛋白免疫印迹法检测海马Iba-1、GFAP、SYN1、PSD-95的表达;荧光定量PCR法检测海马SYN1、PSD-95 mRNA的表达。结果:造模3周末,模型组小鼠体质量、糖水偏好率、移动总距离、直立次数、中央区停留时间均低于正常组(P<0.05),悬尾不动时间长于正常组(P<0.01);造模7周后,模型组小鼠体质量、糖水偏好率、移动总距离、直立次数、中央区停留时间、平均运动速度均低于正常组(P<0.05),悬尾不动时间均长于正常组(P<0.01);海马TNF-a含量高于正常组(P<0.05);海马CA1、CA3、DG区GFAP MOD值及GFAP蛋白相对表达量均低于正常组(P<0.05);海马CA1、CA3、DG区Iba-1 MOD值及Iba-1蛋白相对表达量均高于正常组(P<0.05);海马SYN1、PSD-95蛋白相对表达量及SYN1、PSD-95mRNA相对表达量均低于正常组(P<0.05)。结论:经过CUMS结合CRS方法造模3周后,小鼠即可出现抑郁样行为,在造模7周后,小鼠的抑郁表现更明显。通过CUMS结合CRS方法制备的抑郁症小鼠模型可能与小鼠海马炎症水平升高,小胶质细胞过度活化、星形胶质细胞数量减少及突触可塑性下降有关。 展开更多
关键词 慢性不可预知温和应激 慢性束缚应激 抑郁症 神经胶质细胞 突触可塑性
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Effects of CUMS combined with CRS on hippocampal glial cells and synaptic plasticity in depressed mice
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作者 LI Xin WANG Qiong-ying +3 位作者 ma zhao-tian SUN Hong-hao YU Xue REN Xiao-qiao 《Journal of Hainan Medical University》 2023年第2期7-15,共9页
Objective:To explore the effects of CUMS combined with CRS on mouse hippocampal glial cells and synaptic plasticity-related proteins. Methods: Forty mice were randomly divided into normal group (n=20) and model group ... Objective:To explore the effects of CUMS combined with CRS on mouse hippocampal glial cells and synaptic plasticity-related proteins. Methods: Forty mice were randomly divided into normal group (n=20) and model group (n=20). The model group used CUMS combined with CRS to prepare a mouse model of depression for 7 weeks. The behavioral evaluation of the mice at 3 weeks and 7 weeks after modeling was performed by sugar water preference test, open field test and tail suspension test. After the experiment, the samples were collected, and the content of TNF-a in the hippocampus of mice was detected by enzyme-linked immunosorbent assay. Immunohistochemical method was used to detect the Iba-1 and GFAP MOD values of mouse hippocampal CA1 area, CA3 area and DG area. Western blot was used to detect the protein expression of Iba-1, GFAP, SYN1 and PSD-95 in the hippocampus. fluorescence quantitative PCR method was used to detect the expression of SYN1, PSD-95 mRNA in hippocampus. Results: At the 3rd week after modeling, the body weight, sugar water preference rate, total distance moved, number of standing uprights, and stay time in the central area of the mice in the model group were all lower than those in the normal group (P<0.05), and the tail suspension immobility time was longer than that in the normal group (P<0.01). After 7 weeks of modeling, the body weight, sugar water preference rate, total distance moved, number of erection times, central area residence time, and average movement speed of the mice in the model group were lower than those in the normal group (P< 0.05), the tail suspension immobility time was longer than that in the normal group (P<0.01). The contents of TNF-a in the hippocampus were higher than those in the normal group (P<0.05). The GFAP MOD value and the relative expression of GFAP protein in hippocampal CA1, CA3 and DG regions were significantly lower than those in the normal group (P<0.05). The Iba-1 MOD value and the relative expression of Iba-1 protein in hippocampal CA1, CA3 and DG regions were significantly higher than those in the normal group (P<0.05). The relative expression of SYN1 and PSD-95 protein and the relative expression of SYN1 and PSD-95 mRNA in the hippocampus were significantly lower than those in the normal group (P<0.05). Conclusion: After 3 weeks of CUMS and CRS modeling, the depression-like behavior of mice appeared, and the depression of mice was more obvious after 7 weeks of modeling. The depression mouse model made by CUMS combined with CRS method may be related to increased hippocampal inflammation, excessive activation of microglia, decreased number of astrocytes and decreased synaptic plasticity. 展开更多
关键词 Chronic unpredictable mild stress Chronic restraint stress Depression Neuroglial cell Synaptic plasticity
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