Departments of Pharmacology, Faculty of Medicine, Minia University, 61511 Minia, Egypt.
Department of Histology and Cell Biology, Faculty of Medicine, Minia University, 61511 Minia, Egypt.
Int Immunopharmacol. 2021 Dec;101(Pt A):108174. doi: 10.1016/j.intimp.2021.108174. Epub 2021 Oct 1.
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes long-lasting inflammation on the innermost lining of the colon and rectum. Mirtazapine (MRT) is a well-known antidepressant that was proven to have anti-inflammatory activity; however, to date, its role has not been investigated in UC. The current study aimed to investigate the role and mechanism of MRT in UC.
Acetic acid (AA) was used for UC induction, and sulfasalazine (SLZ) was used as a positive control. Rats were divided into five equal groups; as follows; normal control, AA, SLZ (received SLZ in a dose of 250 mg/kg for 14 days), MRT10 (received MRT in a dose of 10 mg/kg/day for 14 days), and MRT30 (received MRT in a dose of 30 mg/kg/day for 14 days) groups. Macroscopic and microscopic examinations together with oxidative stress parameters evaluation were done. NOD-like receptors-3 (NLRP3), caspase-1, TNF-α, and nuclear factor kappa B (NF-κB) expression together with interleukin (IL)-1β and IL-18 levels were examined.
MRT, in a dose-dependent manner, prevented the macroscopic and microscopic colonic damage and corrected the oxidative stress induced by AA. Moreover, MRT decreased the colonic tissue NLRP3 inflammasome, caspase-1, NF-κB, TNF-α expressions, IL-1β, and IL-18 levels that were elevated in colonic tissue by the AA.
MRT has a dose-dependent protective effect against UC that was mediated mainly by its anti-inflammatory activity with modulation of NLRP3/caspase-1 inflammatory pathway.
溃疡性结肠炎（UC）是一种炎症性肠病（IBD），会导致结肠和直肠的内层长期发炎。米氮平（MRT）是一种众所周知的抗抑郁药，已被证明具有抗炎活性；然而，迄今为止，其在 UC 中的作用尚未得到研究。本研究旨在探讨 MRT 在 UC 中的作用和机制。
使用乙酸（AA）诱导 UC，并使用柳氮磺胺吡啶（SLZ）作为阳性对照。将大鼠分为五组，分别为正常对照组、AA 组、SLZ 组（接受 SLZ 剂量为 250mg/kg，连续 14 天）、MRT10 组（接受 MRT 剂量为 10mg/kg/天，连续 14 天）和 MRT30 组（接受 MRT 剂量为 30mg/kg/天，连续 14 天）。进行宏观和微观检查以及氧化应激参数评估。检测 NOD 样受体-3（NLRP3）、半胱天冬酶-1、肿瘤坏死因子-α（TNF-α）和核因子 kappa B（NF-κB）的表达以及白细胞介素（IL）-1β和 IL-18 水平。
MRT 以剂量依赖的方式预防了 AA 诱导的宏观和微观结肠损伤，并纠正了 AA 引起的氧化应激。此外，MRT 降低了结肠组织 NLRP3 炎性小体、半胱天冬酶-1、NF-κB、TNF-α 的表达以及 IL-1β和 IL-18 水平，这些水平在 AA 处理的结肠组织中升高。
MRT 对 UC 具有剂量依赖性的保护作用，主要通过其抗炎活性介导，通过调节 NLRP3/半胱天冬酶-1 炎症途径。
