Objective

Inflammatory bowel diseases (IBD) are chronic and recurrent disorders of the gastrointestinal tract with unknown etiology and have two major forms, ulcerative colitis (UC) and Crohn diseases. In view of the adverse effects and incomplete efficacy of currently administered drugs, it is essential to investigate new and harmless drugs with more desirable beneficial effects. Statins have many additional pleiotropic effects other than their lipid-lowering effect. This study aims to investigate the role of simvastatin (SIM) at different doses against induced UC in rats.

Methods

SIM (10, 20 mg/kg), and sulfasalazine as a standard therapy (100 mg/kg) were given from five days before and seven days after induction of UC by acetic acid (AA). Colonic mucosal inflammation was evaluated macroscopically and microscopically. Furthermore, the colonic tissue tumor necrosis factor-α (TNF-α), interleukin 1beta (IL 1B), nod-like receptor family pyrin domain-1 containing 3 (NLRP3), malondialdehyde (MDA), reduced glutathione (GSH) and super oxide dismutase (SOD) were assayed in addition to immunohistochemistry of caspase-1 and cyclooxygenase-2 (COX2).

Results

SIM in a dose dependant manner significantly improved macroscopic and histological scores, diminished colonic levels of IL 1B, TNF-α, NLRP3, MDA, caspase-1 and COX2 and elevated GSH and SOD.

Conclusion

SIM has anti-inflammatory, cytoprotective and antioxidants effects that are not directly related to its cholesterol lowering activity against AA induced colitis this makes it a new therapeutic target for UC.

中文翻译：

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辛伐他汀与柳氮磺胺吡啶对乙酸诱导的成年大鼠溃疡性结肠炎的可能改善作用

客观的

炎症性肠病（IBD）是胃肠道病的慢性和复发性疾病，病因不明，有两种主要形式，溃疡性结肠炎（UC）和克罗恩病。考虑到当前施用药物的不良作用和不完全功效，研究具有更理想的有益作用的新的无害药物至关重要。他汀类药物除了具有降脂作用外，还具有许多其他的多效性作用。本研究旨在探讨不同剂量的辛伐他汀（SIM）对大鼠诱导性UC的作用。

方法

SIM（10，20 mg / kg）和柳氮磺胺吡啶作为标准疗法（100 mg / kg）从醋酸（AA）诱导UC的前五天和后七天开始服用。肉眼和显微镜评估结肠粘膜炎症。此外，结肠组织肿瘤坏死因子-α（TNF- α），白介素1β（IL 1B），含3的nod-like受体家族的吡啶域1（NLRP3），丙二醛（MDA），还原型谷胱甘肽（GSH）和超级除了对caspase-1和环氧合酶2（COX2）进行免疫组织化学分析外，还检测了氧化歧化酶（SOD）。

结果

SIM以剂量依赖性方式显着改善了宏观和组织学评分，降低了IL 1B，TNF- α，NLRP3，MDA，caspase-1和COX2的结肠水平，并升高了GSH和SOD。

结论

SIM具有抗炎，细胞保护和抗氧化剂的作用，与降低胆固醇对AA引起的结肠炎的活性没有直接关系，这使其成为UC的新治疗靶标。