褪黑激素对慢性应激性抑郁症大鼠前脑皮质BDNF,TrkB表达及认知行为的影响  

Effects of melatonin on expression of BDNF and TrkB in cerebral cortex and changes of cognitive-behaviors in model rats with chronic mild stress depressant

作　　者：张大鹏[1] 许豪勤 陈艳 许庆 张晔[1] 徐金[1] 周志强[1] 刘益仁[1] 狄荣科[1] 

机构地区：[1]江苏大学基础医学与医学技术学院,江苏镇江212013 [2]镇江市人口与计划生育委员会,江苏镇江212001

出　　处：《江苏大学学报（医学版）》2009年第1期1-4,F0002,共5页Journal of Jiangsu University：Medicine Edition

基　　金：镇江市社会发展基金资助项目(SH2005053)

摘　　要：目的：通过观察慢性应激对大鼠认知行为的变化和前脑皮质BDNF，TrkB表达的影响，探讨褪黑激素抗抑郁作用及其机制。方法：60只SD大鼠，分为5组：空白对照组、模型对照组、褪黑激素治疗Ⅰ-Ⅲ组，每组12只。采用慢性轻度不可预见性应激和孤养方法制作抑郁症模型，腹腔注射褪黑激素加以干预，以＂T＂型迷宫试验和开场试验观察实验前后动物学习记忆能力和探究行为的变化，用免疫组化法测定前脑皮质BDNF，TrkB的表达。结果：应激刺激后，＂T＂型迷宫试验中模型对照组的错误次数多于空白对照组（P〈0.01）和褪黑激素治疗组（P〈0.01），开场试验中模型对照组的水平和直立活动次数少于空白对照组（P〈0.01）和褪黑激素治疗组（P〈0.01/P〈0.05）。前脑各层面皮质均可见到BDNF，TrkB染色阳性细胞，模型对照组阳性细胞及其灰度少于空白对照组和褪黑激素治疗组（P〈0.05/P〈0.01），褪黑激素治疗组则多于空白对照组（P〈0.01）。结论：褪黑激素能有效地促进前脑皮质神经元表达BDNF，TrkB，推测褪黑激素可能通过增强神经营养素，从而起到抑制抑郁症发作的作用。Objective： To explore the anti-depression effect and its mechanism of melatonin（MT）,the changes of cognitive-behavior and expressions of BDNF and TrkB in rat cerebral cortex with chronic stress depression.Methods： Sixty SD rats were divided into five groups： blank control group,depression model control group,MT treated groups Ⅰ-Ⅲ.The depression model was induced by the chronic unpredictability mild stress（CUMS） and isolated breeding.The depression model rats were treated with melatonin by intraperitoneal injection after chronic stress stimulation.Before and after the experiment,T-type labyrinth test and Open-fields test were used for observation of learning and memory and changes in explored behavior in animals.The expression level of BDNF and TrkB in cerebral cortex was analyzed by immunohistochemistry determination. Results： After chronic stress stimulation,the fault frequency of the T-type labyrinth test in depression model control group was more than that in the blank control group（P〈0.05） and MT treated groups（P〈0.01）.The activity frequency of the open-fields test in depression model group was less than that in the blank control group and MT treated groups.BDNF and TrkB positive cells were observed in each section of cerebral cortex of rat′s forebrain,but the numbers of positive cells and their gray scales on the depression model control group were less than those in the blank control group and MT treated group.Moreover,compared with those indexes,MT treated groups were more than those in the blank control group. Conclusion： Melatonin can be effective in promoting neurons of cerebral cortex to express BDNF and TrkB.Melatonin can relieve the injury from the chronic mild stress stimulation by enhancing the nervous protection of nutrients to play the role of antidepressant.

关 键 词：抑郁症 褪黑激素 慢性轻度应激 脑源性神经营养因子 酪氨酸激酶B 

分 类 号：R322.81[医药卫生—人体解剖和组织胚胎学]