维生素B12对抑郁大鼠行为学和脑单胺类神经递质及脑源性神经营养因子的影响  

Effects of Vitamin B12 on Behaviors,Brain Monoamine Neurotransmitters,and Brain-Derived Neurotrophic Factor in Depressive Rats

作　　者：陈晶[1] 刘瑾春 张鹏杰 张申起[3] CHEN Jing;LIU Jinchun;ZHANG Pengjie;ZHANG Shenqi(Department of Clinical Medicine,Henan Vocational College of Nursing,Anyang 455000,China;The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China;Department of Neurosurgery,Renmin Hospital of Wuhan University and Hubei General Hospital,Wuhan 430000,China)

机构地区：[1]河南护理职业学院临床医学系,安阳455000 [2]郑州大学第一附属医院,郑州450000 [3]武汉大学人民医院神经外科,武汉430000

出　　处：《四川大学学报(医学版)》2025年第1期206-214,共9页Journal of Sichuan University(Medical Sciences)

基　　金：河南省高等学校重点科研项目(No.22B310001);湖北省自然科学基金面上项目(No.2020CFB638)资助。

摘　　要：目的研究慢性不可预测温和应激(chronic unpredictable mild stress,CUMS)抑郁模型大鼠行为学及单胺类神经递质含量的变化,探讨维生素B12(VitB12)对CUMS大鼠可能的作用及其关系。方法将72只SD大鼠随机分为对照组(Control组)、CUMS组(接受3周慢性不可预测温和应激)和CUMS+VitB12组(CUMS大鼠颈部注射微量VitB12)。对3组大鼠体质量测量,并采用糖水偏好实验、旷场实验和强迫游泳等方法对大鼠进行行为学检测;高效液相色谱法(HPLC)分析各组大鼠单胺类神经递质,包括5-羟色胺(5-HT)、去甲肾上腺素(NE)和多巴胺(DA)含量的变化;苏木素-伊红(HE)染色观察海马神经元病理学变化;蛋白免疫印迹法(Western blot)检测海马组织中脑源性神经营养因子(BDNF)/酪氨酸激酶受体TrkB/环磷腺苷效应元件结合蛋白(CREB)信号通路相关蛋白表达。结果第5周开始,CUMS组大鼠较对照组平均体质量降低,CUMS+VitB12组大鼠较CUMS组平均体质量增加(均P<0.05)。在第3周和第6周,CUMS组大鼠对糖水偏好均低于对照组(P<0.001);CUMS+VitB12组糖水消耗量较CUMS组有所升高,且第6周升高水平更明显(P<0.01,P<0.001)。第4周开始,旷场实验中CUMS组大鼠穿格、修饰和站立得分较对照组均降低(P<0.001);CUMS+VitB12组大鼠较CUMS组运动能力和探索能力有所改善(P<0.01,P<0.001)。第3周和第6周强迫游泳实验中,CUMS组大鼠较对照组静止时间延长(P<0.01);第6周,CUMS+VitB12组大鼠静止的时间相较CUMS组缩短(P<0.01)。HPLC结果显示,CUMS组大鼠大脑皮质5-HT、NE、DA含量较对照组下降(P<0.01,P<0.001);CUMS+VitB12组较CUMS组5-HT、NE、DA含量升高(P<0.05,P<0.01)。HE染色检测结果显示,CUMS组大鼠海马组织细胞数量较对照组明显减少;CUMS+VitB12组大鼠海马组织小较CUMS组数量增多,形态饱满光滑(P<0.05)。Western blot结果显示,CUMS组大鼠海马组织BDNF、TrkB和CREB蛋白表达较对照组降低(P<0.05),CUMS+VitB12组大鼠海马Objective To investigate the behavioral changes and monoamine neurotransmitter levels in a rat model of chronic unpredictable mild stress(CUMS)-induced depression and explore the potential effects of Vitamin B12(VitB12)on CUMS model rats and the underlying mechanisms.Methods A total of 72 Sprague-Dawley(SD)rats were randomly assigned to 3 groups,a control group,a CUMS group(subjected to three weeks of CUMS),and a CUMS+VitB12 group(CUMS rats receiving microinjections of VitB12 in the neck).The body mass of the rats was measured,and behavioral assessments were conducted using the sucrose preference test,open field test,and forced swimming test.Highperformance liquid chromatography(HPLC)was used to analyze the levels of monoamine neurotransmitters,including 5-hydroxytryptamine(5-HT),norepinephrine(NE),and dopamine(DA),in each group of rats.Hematoxylin-eosin(HE)staining was performed to observe pathological changes in hippocampal neurons.Western blot was performed to detect the expression of signal pathway-related proteins,including brain-derived neurotrophic factor(BDNF),tropomyosin receptor kinase B(TrkB),and cyclic adenosine monophosphate(cAMP)response element-binding protein(CREB)in the hippocampal tissue.Results Starting from week 5,rats in the CUMS group exhibited lower average body mass compared to the control group,while the CUMS+VitB12 group showed a significant increase in body mass compared to the CUMS group(P<0.05).At weeks 3 and 6,sucrose preference of rats in the CUMS group was significantly lower than that in the control group(P<0.001).At week 3,sucrose consumption in the CUMS+VitB12 group was significantly higher than that in the CUMS group(P<0.01),with a more pronounced increase observed in week 6(P<0.001).Starting from week 4,the CUMS group showed reduced scores in grid crossing,grooming,and rearing activities in the open field test compared to the control group,indicating reduced locomotor activity and exploratory behavior(P<0.001).The CUMS+VitB12 group showed improved behavioral performance compar

关 键 词：抑郁症 大鼠模型 行为学 单胺类神经递质 脑源性神经营养因子 

分 类 号：R749.4[医药卫生—神经病学与精神病学]