Qiu Hong-Mei, Yang Jun-Xia, Jiang Xin-Hui, Hu Xiao-Ya, Liu Dan, Zhou Qi-Xin
Departments of aPharmacology bDrug Analysis, Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy of Chongqing Medical University, Chongqing, China.
Neuroreport. 2015 Dec 16;26(18):1145-50. doi: 10.1097/WNR.0000000000000482.
Depression is a common worldwide mental disorder whose etiology remains unclear; there is also a lack of effective therapeutic agents. Sodium valproate (VPA) is a traditional antiepileptic drug with mood-stabilization effect and is increasingly being used to treat bipolar disorders and depression, but its antidepressant mechanism remains unknown. The aim of the present study was to investigate the possible mechanisms of antidepressant action by studying malondialdehyde level, catalase, and superoxide dismutase activities in the serum and the mRNA and protein expression of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) in the prefrontal cortex of rats exposed to chronic unpredicted stress (CUS). Male Sprague-Dawley rats were used to establish a depression model by CUS. VPA (300 mg/kg once daily) and an equivalent volume of vehicle were administered to rats by an intragastric gavage. Rat behaviors, serum malondialdehyde level, serum catalase and superoxide dismutase activities, and the mRNA and protein expressions of TH and TPH in the prefrontal cortex were determined. The results showed that VPA treatment led to a significant decrease in depression-like behaviors, improvement in oxidative stress imbalance, and enhancement of TH, TPH mRNA, and protein expression in stressed rats, but failed to show any significant changes in control rats. This could indicate that the antidepressant mechanism of VPA is perhaps linked to upregulation of TH and TPH expression and inhibition of oxidative damage in CUS rats.
抑郁症是一种常见的全球性精神障碍，其病因尚不清楚；目前也缺乏有效的治疗药物。丙戊酸钠（VPA）是一种具有情绪稳定作用的传统抗癫痫药物，越来越多地被用于治疗双相情感障碍和抑郁症，但其抗抑郁机制仍不清楚。本研究的目的是通过研究慢性不可预测应激（CUS）大鼠血清中的丙二醛水平、过氧化氢酶和超氧化物歧化酶活性，以及前额叶皮质中酪氨酸羟化酶（TH）和色氨酸羟化酶（TPH）的mRNA和蛋白表达，来探讨VPA抗抑郁作用的可能机制。采用雄性Sprague-Dawley大鼠通过CUS建立抑郁症模型。通过灌胃给予大鼠VPA（300 mg/kg，每日一次）和等量的溶剂。测定大鼠行为、血清丙二醛水平、血清过氧化氢酶和超氧化物歧化酶活性，以及前额叶皮质中TH和TPH的mRNA和蛋白表达。结果表明，VPA治疗可显著减少应激大鼠的抑郁样行为，改善氧化应激失衡，并增强TH、TPH mRNA和蛋白表达，但对对照大鼠未显示任何显著变化。这可能表明，VPA的抗抑郁机制可能与上调CUS大鼠中TH和TPH的表达以及抑制氧化损伤有关。
