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帕罗西汀在大鼠模型中的抗抑郁作用:上调5-羟色胺和去甲肾上腺素转运体的表达

Antidepressive effect of paroxetine in a rat model: upregulating expression of serotonin and norepinephrine transporter.

作者信息

Qiu Hong-Mei, Yang Jun-Xia, Wu Xiao-Hong, Li Na, Liu Dan, Wang Li-Jia, Qin Li-Juan, Zhou Qi-Xin

机构信息

Key Laboratory of Biochemistry and Molecular Pharmacology, Department of Pharmacology, School of Pharmacy of Chongqing Medical University, Chongqing, China.

出版信息

Neuroreport. 2013 Jul 10;24(10):520-5. doi: 10.1097/WNR.0b013e328362066d.

Abstract

Paroxetine is a selective serotonin reuptake inhibitor used for the treatment of depression; this study investigated its other mechanisms by studying the expression and therefore involvement of norepinephrine transporter (NET) and serotonin transporter (5-HTT). Male Sprague-Dawley rats were divided into a vehicle-treated control group (VC), a paroxetine-treated control group (PC), a vehicle-treated model group (VM), and a paroxetine-treated model group (PM). The depression model was established by chronic unpredicted stress. Paroxetine (1.8 mg/kg once daily) was administered to rats (PM and PC groups) by an intragastric gavage, and the same dosage of vehicle was administered to rats in the VM and VC groups. Rat behaviors, superoxide dismutase and catalase activities, malondialdehyde level in the serum, and expression of 5-HTT in the hippocampus and NET in the pons were determined, respectively. Compared with VM rats, the PM rats showed significant relief of depression-like behaviors, decrease in the malondialdehyde level, increase in superoxide dismutase and catalase activities, and increase in 5-HTT and NET expression. The results may suggest that the antidepressive effect of paroxetine is at least partly related to reversing oxidative stress imbalance and elevating the expression of 5-HTT and NET.

摘要

帕罗西汀是一种用于治疗抑郁症的选择性5-羟色胺再摄取抑制剂;本研究通过研究去甲肾上腺素转运体(NET)和5-羟色胺转运体(5-HTT)的表达及其参与情况,对其其他作用机制进行了研究。将雄性Sprague-Dawley大鼠分为溶剂对照组(VC)、帕罗西汀治疗对照组(PC)、溶剂处理模型组(VM)和帕罗西汀治疗模型组(PM)。通过慢性不可预测应激建立抑郁症模型。通过灌胃法给大鼠(PM组和PC组)施用帕罗西汀(每日一次,1.8mg/kg),给VM组和VC组大鼠施用相同剂量的溶剂。分别测定大鼠行为、超氧化物歧化酶和过氧化氢酶活性、血清中丙二醛水平以及海马体中5-HTT的表达和脑桥中NET的表达。与VM组大鼠相比,PM组大鼠的抑郁样行为明显缓解,丙二醛水平降低,超氧化物歧化酶和过氧化氢酶活性增加,5-HTT和NET表达增加。结果可能表明,帕罗西汀的抗抑郁作用至少部分与逆转氧化应激失衡以及提高5-HTT和NET的表达有关。

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