首页|脑源性神经营养因子介导卒中后抑郁的病理机制研究

脑源性神经营养因子介导卒中后抑郁的病理机制研究

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目的 探讨脑源性神经营养因子(BDNF)在卒中后抑郁(PSD)中的神经保护作用.方法 采用目前公认的大脑中动脉闭塞法(MCAO),建立C57BL/6J小鼠脑卒中模型,磁共振成像(MRI)在活体状态下检测小鼠脑区呈像.以糖水偏爱试验(SPT)和旷场试验(OFT)行为学评定,筛选出抑郁状态的小鼠作为PSD模型.在对照组、MCAO组和PSD组进行原位缺口末端标记法(TUNEL)染色和FJ-C染色观察3组小鼠在不同脑区发生凋亡或变性的神经元.蛋白质印迹法(Western blot)检测对照组、MCAO组、抑郁组和PSD组BDNF蛋白表达情况.结果 MRI检查MCAO术后7 d小鼠脑区成像,显示在皮层、海马和纹状体均有不同程度的脑水肿,FJ-C染色显示在不同脑区均有绿色标记阳性的变性细胞.对照组小鼠无阳性标记的细胞,MCAO术后3周和PSD组均有TUNEL红色标记阳性的凋亡细胞和FJ-C标记阳性的变性细胞,PSD组小鼠发生凋亡和变性的神经元细胞数量较MCAO组小鼠显著增多,以海马区最为显著.PSD组小鼠BDNF蛋白表达水平显著低于MCAO组(t=2.898,P＜0.01).结论 BDNF在卒中后抑郁表达减少,进而影响海马神经发育和突触可塑性.
Pathological mechanisms of brain-derived neurotrophic factor-mediated post-stroke depression
Objective To explore the neuroprotective effects of brain-derived neurotrophic factor(BDNF)on post-stroke depression(PSD).Methods Ischemic stroke mouse model was established using middle cerebral artery occlusion(MCAO)on C57BL/6J mice.Magnetic resonance imaging(MRI)was used to detect the cerebral area of the rats in vivo.Mice with depression were selected as PSD models by the behavioral evaluation of sucrose preference test(SPT)and open-field test(OFT).Terminal-deoxynu-cleotidyl transferase mediated nick end labeling(TUNEL)staining and FJ-C staining were performed in control group,MCAO group and PSD group to observe apoptosis or degeneration of neurons in different brain regions.Western blotting was used to detect the expression of BDNF protein in control group,MCAO group,depression group and PSD group.Results MRI was performed 7 days after MCAO modeling.The results showed different degrees of cerebral edema in cortex,hippocampus and striatum,and FJ-C staining showed positive green marked degenerative cells in different brain areas.There were no positive labeled cells in the control group,and apoptotic cells with TUNEL red labeling positive and FJ-C green labeling positive were found in both the MCAO group and the PSD group.Meanwhile,the number of apoptotic and degenerated neurons in the PSD group was significantly increased as compared with the MCAO group,espe-cially in the hippocampus.The expression of BDNF protein in PSD group was significantly lower than that in the MCAO group(unpaired t-test,t=2.898,P＜0.01).Conclusion The expression of BDNF is de-creased in PSD,which further affects hippocampal neurodevelopment and synaptic plasticity.

Post-stroke depressionIschemic strokeBrain-derived neurotrophic factorHippocampus

韦娜、张罗曼、黄会粉、任华艳、何欣、薛瑞、许晶晶、刘宏建

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郑州大学第一附属医院病理科医学部,郑州 450002

郑州大学基础医学院病理学系,郑州 450002

郑州大学第一附属医院医学研究中心,郑州 450002

郑州大学第一附属医院骨科医学部,郑州 450002

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卒中后抑郁 缺血性卒中 脑源性神经营养因子 海马

河南省科技攻关计划河南省科技攻关计划河南省科技攻关计划河南省医学科技攻关计划河南省高等学校重点科研项目郑州大学青年教师培育基金

222102310084202102310354182102310512SBGJ20210305223A310003JC23862068

2024

10.3760/cma.j.cn421213-20230920-01334

中华实验外科杂志
中华医学会

中华实验外科杂志

CSTPCD
影响因子：0.759
ISSN：1001-9030
年,卷(期)：2024.41(4)
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