【作者】 王艳；

【导师】 刘继文；

【作者基本信息】 新疆医科大学 ， 劳动卫生与环境卫生学， 2007， 硕士

【摘要】 目的:通过建立慢性不可预知的温和应激抑郁模型(Chronic unpredictablemild stress,CUMS),观察大鼠出现抑郁状态后的行为学改变,S100β、胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)和c-fos蛋白在抑郁大鼠海马区的表达以及慢性温和应激对大鼠学习、记忆功能的影响,探讨它们在抑郁发生、发展过程中的作用及其意义。方法:选用Wister成年雄性大鼠30只,根据敞箱实验得分随机分为模型组和正常对照组,模型组连续8周采用单笼饲养和慢性不可预知的温和应激造模,观察大鼠体重变化、行为改变、血浆皮质酮水平、血浆和脑匀浆S100β蛋白水平以及海马超微结构的改变,用大鼠跳台仪测试大鼠的学习记忆能力,同时用免疫组织化学方法检测海马区S100β、GFAP和c-fos蛋白的表达。结果:(1)模型组大鼠体重增长减慢,大脑系数降低(P＜0.01),血浆皮质酮水平升高(P＜0.01);(2)模型组大鼠水平运动、垂直运动得分显著下降,清洁动作次数减少,糖水消耗和糖水偏爱百分比较正常对照组下降(P＜0.01),跳台实验结果显示模型组大鼠反应期延长,潜伏期缩短,错误次数增加;(3)模型组大鼠海马形态结构改变,超微结构异常;(4)模型组大鼠血浆S100β水平高于正常对照组(P＜0.05),海马区S100β、GFAP蛋白表达增加,c-fos蛋白表达减少;(5)S100β和GFAP蛋白表达与大鼠学习记忆能力负相关(P＜0.05),S100β表达与GFAP数目正相关(r=0.739,P＜0.01),S100β和c-fos蛋白表达无相关,GFAP和c-fos蛋白表达无相关。结论:慢性不可预知的温和应激可诱发实验大鼠较长时间的行为及活动习性的改变,并可损伤海马,通过S100β、GFAP蛋白表达的增加以及c-fos蛋白表达减少,影响大鼠的学习记忆功能,从而促进心理障碍疾病的发生、发展。更多还原

【Abstract】 Objective:To establish a model of chronic unpredictable mild stress(CUMS), and then to observe behavior changes,the expression of S100β,GFAP and c-fos in hippocampus and memory function in depression rats,to explore their mechanism in the development of depression.Methods:Thirty male Wistar rats were divided into control group and stress group.Depression model was established by using chronic unpredictable mild stress stimulation combined with lonely raising for eight weeks.Weight and behavior changes were observed,plasma levels of cortisol were measured by radioimmune assay and S100βprotein concentrations were measured using enzyme linked immuno-absorbent assay.Platform test was used to observe learning and memory function and the expression of S100β,GFAP and c-fos protein in hippocampus were detected by immunohistochemistry.Results:(1)Compared with control group, weight and organic coefficient of brain decreased in model group(P＜0.01),but plasma corticosterone levels increased significantly(P＜0.01).(2)Compared with control group, it was decreased significantly in the crossing and rearing movement times,clean times, the volume of sucrose-intake and the preference of sucrose in model group(P＜0.01).The platform test suggested that the reaction time in model group was prolonged significantly than that of the control,the pre-reaction time was shorten obviously,and the error frequence was increased in model group.(3)The ultrastructure changes in the hippocampus were observed by electron microscope.(4)Plasma concentrations of S100βprotein in model group were higher than that of the control group(P＜0.05),and the expression of S100βand GFAP protein in the hippocampus were increased,but the expression of c-fos decreased.(5)An increase of expression of S100βand GFAP protein were negatively correlated to decline of learning and memory function(P＜0.05).The expression of S100βprotein was positively correlated to GFAP expression(r=0.739, P＜0.01),but the expression of c-fos protein had no correlation to S100βand GFAP. Conclusions:The repeated chronic unpredictable mild stress stimulation can induce long-time changes in acts and activities and damage the hippocampus structure of rats. The chronic mild stimulation can induce an increase of expression of S100βand GFAP and an decrease of c-fos in rat hippocampus.It can also affect learning and memory function of rats,which may play an important role of mental disorder.更多还原