Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627-Pampulha, Belo Horizonte, Minas Gerais, CEP 31270-901, Brazil.
Department of Pathology, University of Massachusetts Medical School, 368 Plantation St, Worcester, MA, United States.
Inflammation. 2021 Apr;44(2):580-591. doi: 10.1007/s10753-020-01356-0. Epub 2020 Oct 9.
Recent data has signaled that in addition to its therapeutic indications as antidepressant and analgesic, amitriptyline (AM) exerts anti-inflammatory effects in humans and experimental animal models of acute inflammation. We tested the hypothesis that this compound could also modulate the chronic inflammatory process induced by synthetic matrix in mice. Polyether-polyurethane sponge disks were implanted subcutaneously in 9-week-old male C57BL/6 mice. The animals received by oral gavage 5.0 mg/kg of amitriptyline for seven consecutive days in two treatment regimens. In the first series, the treatment was initiated on the day of surgery and the implants removed at day 7 post-implantation. For the assessment of the effect of amitriptyline on chronic inflammation, the treatment was initiated 7 days post-implantation and the sponge discs removed 14 after implantation. The inflammatory markers evaluated, myeloperoxidase - MPO, nitrite content, IL-6, IFN-γ, TNF-α, CXCL1 and CCL2 levels, and NF-κB transcription factor activation were reduced in implants when the treatment began 7 days post-implantation (chronic inflammation). In contrast, only mast cell number, MPO activity and activation of NF-κB pathway decreased when the treatment began soon after implantation (sub-acute inflammation) in 7-day old implants. The anti-inflammatory effects of amitriptyline described here, extend its range of actions as a potential agent able to attenuate long-term inflammatory processes.
最近的数据表明，阿米替林（AM）除了作为抗抑郁药和镇痛药的治疗适应症外，在人类和急性炎症的实验动物模型中还具有抗炎作用。我们检验了这样一个假设，即这种化合物也可以调节由合成基质在小鼠中引起的慢性炎症过程。聚醚-聚亚安酯海绵片被植入 9 周龄雄性 C57BL/6 小鼠的皮下。动物通过口服灌胃给予 5.0mg/kg 的阿米替林，连续 7 天，分为两种治疗方案。在第一个系列中，治疗从手术当天开始，植入物在植入后第 7 天取出。为了评估阿米替林对慢性炎症的影响，治疗从植入后第 7 天开始，植入物在植入后 14 天取出。在开始治疗后 7 天（慢性炎症）时，植入物中的髓过氧化物酶-MPO、亚硝酸盐含量、IL-6、IFN-γ、TNF-α、CXCL1 和 CCL2 水平以及 NF-κB 转录因子的激活等炎症标志物降低。相反，当治疗在植入后 7 天（亚急性炎症）时立即开始时，只有肥大细胞数量、MPO 活性和 NF-κB 途径的激活降低。阿米替林的这种抗炎作用扩展了其作为一种潜在的能够减轻长期炎症过程的药物的作用范围。
