CUS致大鼠抑郁行为涉及单胺递质合成酶表达下调  

Down-regulation of monoamine neurotransmitter synthetase expression involved in CUS-induced depression of rats

作　　者：汪丽佳 邱红梅 蒋心惠 刘丹[2] 费慧芝 胡小娅 周岐新 

机构地区：[1]重庆市生物化学和分子药理学重点实验室,重庆400016 [2]重庆市中山医院,重庆400015 [3]重庆市三峡医学高等专科学校,重庆404100

出　　处：《中国药理学通报》2015年第4期527-531,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 31400881);重庆市教委科学技术研究项目(No KJ1400208)

摘　　要：目的探讨慢性不可预知性刺激(chronically unpredicted stress,CUS)致大鼠抑郁行为与单胺递质合成限速酶色氨酸羟化酶(tryptophan hydroxylase,TPH)和酪氨酸羟化酶(tyrosine hydroxylase,TH)表达的关系。方法♂SD大鼠30只,随机分为对照组(control group,CG)和模型组(model group,MG),每组15只。采用连续给予CUS结合孤养28 d建立抑郁模型;对照组每笼5只,正常饲养;以开场试验和糖水消耗实验进行行为学评价;以荧光定量PCR测定海马、前脑皮层TPH及TH mRNA表达,以Western blot法测定海马、前脑皮层TPH及TH蛋白表达。结果与CG相比,MG大鼠开场实验水平和垂直活动得分均明显降低,糖水消耗量也显著减少,海马、前脑皮层TPH及TH mRNA和蛋白表达均明显下降。结论 CUS诱导♂大鼠产生抑郁症样行为,其发生机制可能与单胺递质合成限速酶TPH、TH表达下调相关。Aim To investigate whether chronically unpredictable stress（ CUS）-induced depression-like behaviors of rats is associated with the variant expression of tryptophan hydroxylase（ TPH） and tyrosine hydroxylase（ TH）. Methods 30 male SD rats were randomly divided into depression model group（ MG） and control group（ CG）,the former was established using CUS plus solitary condition for 28 d,whereas the latter was fed normally as five rats per cage without CUS.The open field test（ OFT） and the sucrose preference test were used to evaluate depressive behaviors. Both mRNA and protein expressions of TPH and TH in hippocampus and forebrain cortex were determined by real-time fluorescent quantitative PCR and western blot（ WB）,respectively. Results MG rats showed obvious depressive behaviors with much lower locomotive activity and sucrose preference than CG. Meanwhile,the mRNA and protein expressions of TPH and TH also significantly decreased in MG rats,compared with CG rats. Conclusion The depression behaviors of rats induced by CUS may be associated with down-regulation of TPH and TH expression.

关 键 词：抑郁症 慢性不可预见性刺激 色氨酸羟化酶 酪氨酸羟化酶 5羟色胺 去甲肾上腺素 

分 类 号：R332[医药卫生—人体生理学] R322.81[医药卫生—基础医学]