Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Graduate School, Chiang Mai University, Chiang Mai, 50200, Thailand.
Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Eur J Pharmacol. 2020 May 5;874:173028. doi: 10.1016/j.ejphar.2020.173028. Epub 2020 Feb 19.
Stroke is a major cause of death and permanent disability worldwide. It has been reported that 85% of stroke patients undergo an ischaemic stroke. The standard treatment is currently recanalization. However, only 5% of patients have access to this treatment. Therefore, new strategies for permanent ischaemic stroke treatment need to be investigated. Agomelatine is a melatonergic agonist that acts on MT1/2 receptors and is an antagonist of 5-HT2c receptors, and melatonergic has pleiotropic effects, such as antioxidation or anti-inflammation effects. In this study, we focused on the effect of agomelatine on permanent cerebral ischaemia in a rat model. Male Wistar rats were randomly divided into the following four groups (n = 6/group): sham operating group, permanent ischaemic model group, permanent ischaemic model plus agomelatine (40 mg/kg, i.p) group and permanent ischaemic model plus melatonin (10 mg/kg, i.p) group. Twenty-four h after ischaemic onset, we investigated the neurological deficits and infarct volume using neurological deficit scores, 2,3,5-triphenyltetrazolium chloride (TTC) and transmission electron microscopy (Kochanski et al.). Moreover, we analysed Nrf2-HO-1 protein expression by Western blot. The results showed that agomelatine and melatonin decreased neuronal injury and promoted the Nrf2-HO-1 signalling pathway. These findings suggest that agomelatine and melatonin exert beneficial effects on permanent cerebral ischaemia.
中风是全球范围内主要的死亡和永久性残疾原因。据报道，85%的中风患者发生缺血性中风。目前的标准治疗方法是再通。然而，只有 5%的患者能够接受这种治疗。因此，需要研究新的治疗永久性缺血性中风的策略。阿戈美拉汀是一种作用于 MT1/2 受体的褪黑素激动剂，也是 5-HT2c 受体的拮抗剂，褪黑素具有多种作用，如抗氧化或抗炎作用。在这项研究中，我们专注于阿戈美拉汀对大鼠永久性脑缺血模型的影响。雄性 Wistar 大鼠随机分为以下四组（每组 n=6）：假手术组、永久性缺血模型组、永久性缺血模型加阿戈美拉汀（40mg/kg，腹腔注射）组和永久性缺血模型加褪黑素（10mg/kg，腹腔注射）组。缺血发作 24 小时后，我们通过神经功能缺损评分、2,3,5-三苯基氯化四氮唑（TTC）和透射电镜（Kochanski 等人）来研究神经功能缺损和梗死体积。此外，我们通过 Western blot 分析 Nrf2-HO-1 蛋白表达。结果表明，阿戈美拉汀和褪黑素可减轻神经元损伤并促进 Nrf2-HO-1 信号通路。这些发现表明阿戈美拉汀和褪黑素对永久性脑缺血具有有益作用。
