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
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篇名: 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
TITLE:
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7 d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(1 min)、频闪照明刺激(120 次/min,12 h)、噪声刺激(4 h)、冰水游泳刺激(1 h)、热水刺激(45 ℃,1 h)、电击足底(10 Hz,1 mA,每次间隔100 ms,100次)、禁食禁水(24 h)],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30 d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。
ABSTRACT: 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 mA, 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 content induced by the decrease of TPH expression in brain tissue of rats, indicating that TPH can be used as a target for depression treatment.
期刊: 2017年第28卷第22期
作者: 陈栘,徐海霞,朱明月,刘坤,林波,罗儒献,陈川柏,李孟森
AUTHORS: CHEN Yi, XU Haixia,ZHU Mingyue,LIU Kun,LIN Bo,LUO Ruxian,CHEN Chuanbai,LI Mengsen
关键字: 抑郁症模型;5-羟色胺;色氨酸羟化酶;大鼠
KEYWORDS: Depression model; 5-hydroxytryptamine; Tryptophan hydroxylase; Rats
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