慢性低强度应激抑郁症模型大鼠组织中5-羟色胺和色氨酸羟化酶的表达变化  

Changes of 5-hydroxytryptamine and Tryptophan Hydroxylase Expressions in Tissues of Depression Model Rats Induced by Chronic Low-intensity Stress

作　　者：陈栘 徐海霞[1,2] 朱明月[1,2] 刘坤[1,2] 林波[1,2] 罗儒献 陈川柏 李孟森[1,2] 

机构地区：[1]海南医学院分子生物学重点实验室,海口571199 [2]海南省肿瘤发生和干预重点实验室,海口571199 [3]海南省安宁医院精神科,海口571199

出　　处：《中国药房》2017年第22期3061-3064,共4页China Pharmacy

基　　金：海南省自然科学基金资助项目(No.812162;813198)

摘　　要：目的:为抑郁症治疗药物的开发提供依据和思路。方法:将适应性喂养7d的大鼠随机分为正常组、抑郁组和治疗组(氢溴酸西酞普兰1 mg/kg),每组8只,抑郁组和治疗组大鼠每天随机给予1次低强度刺激[夹尾刺激(1min)、频闪照明刺激(120次/min,12h)、噪声刺激(4h)、冰水游泳刺激(1h)、热水刺激(45℃,1h)、电击足底(10 Hz,1mA,每次间隔100 ms,100次)、禁食禁水(24h)],连续21 d建立应激抑郁症模型。分别于适应性喂养第0、7天和应激第7、14、21天称量各组大鼠体质量,检测旷场实验中大鼠的水平移动频率和垂直活动频率。应激结束后,各组大鼠ig相应药物,连续30d后检测脑、肝、肾组织中5-羟色胺(5-HT)和色氨酸羟化酶(TPH)的表达。结果:与正常组比较,抑郁组和治疗组大鼠从应激第14天起体质量增加趋势减慢(P<0.05)。抑郁组和治疗组大鼠应激第14、21天的水平移动频率较前一时间点明显降低(P<0.05或P<0.01),应激第21天的垂直活动频率较前一时间点明显降低(P<0.05或P<0.01);给药30 d后,治疗组大鼠水平移动频率和垂直活动频率较前一时间点明显升高(P<0.01)。与抑郁组比较,治疗组大鼠脑、肾组织中的5-HT水平明显增加(P<0.05),脑组织中TPH水平明显增加(P<0.05)。结论:应激大鼠模型抑郁症的发生与大鼠脑组织中TPH表达的降低从而导致5-HT水平降低有关,提示TPH可作为抑郁症治疗的靶点。OBJECTIVE：To provide basis and thinking for the development of medicines for treating depression. METHODS：Rats with adaptive feeding for 7 d were randomly divided into normal group,depression group and treatment group（citalopram hydrobromide 1 mg/kg）,8 in each group. Rats in depression group and treatment groups randomly received once low-density stimulation in a day [catching tail stimulation（1 min）,frequent flashing stimulation（120 times/min,12 h）,noise stimulation（4 h）,ice water swimming stimulation（1 h）,hot water stimulation（45 ℃,1 h）,electric shocking foot（10 Hz,1 m A,each time interval of 100 ms,100 times）,no food and no water（24 h）] for 21 d to reduce stress depression model. Body mass of rats in 0,7 d of adaptive feeding and 7,14,21 d of stress were respectively weighed,and horizontal activity and vertical activity frequencies in open field test were detected. After stress,rats were intragastrically administrated related medicines for 30 d,then 5-hydroxytryptamine（5-HT） and tryptophan hydroxylase（TPH） expressions in brain,liver,kidney tissues were determined. RESULTS：Compared with normal group,the increasing trend of body mass in depression group and treatment group slowed down from the 14 d of stress（P〈0.05）. The horizontal activity frequencies in depression group and treatment group in 14,21 d of stress slowed more obviously than the previous time point（P〈0.05 or P〈0.01）;vertical activity frequencies in 21 d of stress slowed more obviously than the previous time point（P〈0.05 or P〈0.01）. After 30 d of administration,horizontal activity and vertical activity frequencies in treatment group were increased more obviously than the previous time point（P〈0.01）. Compared with depression group,5-HT level in brain,kidney tissues was obviously increased（P〈0.05）and TPH level was obviously increased in brain tissue（P〈0.05）. CONCLUSIONS：The occurrence of depression in stress rat models may be associated with the decrease of 5-HT

关 键 词：抑郁症模型 5-羟色胺 色氨酸羟化酶 大鼠 

分 类 号：R965[医药卫生—药理学]