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.doc

　　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 ：张大鹏, 许豪勤, 陈 艳, 许 庆, 张 晔, 徐金, 周志强, 刘益仁, 狄荣科 【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（Plt;0.01）和褪黑激素治疗组（Plt;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（Plt;0.01）和褪黑激素治疗组（Plt;0.01/Plt;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（Plt;0.05/Plt;0.01），褪黑激素治疗组则多于空白对照组（Plt;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。 【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 ［Abstract］ 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 odel control group, MT treated groups ⅠⅢ. The depression model ild stress (CUMS) and isolated breeding. The depression model rats elatonin by intraperitoneal injection after chronic stress stimulation. Before and after the experiment, Ttype labyrinth test and Openfields test emory and changes in explored behavior in animals. The expression level of BDNF and TrkB in cerebral cortex munohistochemistry determination. Results： After chronic stress stimulation, the fault frequency of the Ttype labyrinth test in depression model control group ore than that in the blank control group (Plt;0.05) and MT treated groups (Plt;0.01). The activity frequency of the openfields test in depression model group bers of positive cells and their gray scales on the depression model control group ore 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. ［Key elatonin; chronic mild stress; brainderived neurotrophic fact