Chen Lu, Zhou Zhongyin, Yang Yan, Chen Na, Xiang Hongyu
Department of Gastroenterology, Hubei Key Laboratory of Digestive System Disease, RenMin Hospital of Wuhan University, Wuhan, China.
PLoS One. 2017 Oct 19;12(10):e0186138. doi: 10.1371/journal.pone.0186138. eCollection 2017.
Imiquimod is a Toll-like receptor-7 agonist that regulates immunity and can be used as an immune adjuvant. Ulcerative colitis has a close correlation with immune disorder.
To investigate the therapeutic effect of imiquimod on dextran sulfate sodium (DSS)-induced colitis and explore the underlying mechanisms.
C57BL/6J C57 mice received 3% DSS for 7 days to induce ulcerative colitis. Groups of mice were intraperitoneally injected with dexamethasone (DXM, 1.5 mg/kg) or imiquimod (IMQ, 30 mg/kg) at the same time daily. During the experimental period, clinical signs, body weight, stool consistency and visible fecal blood were monitored and recorded daily; colitis was evaluated by disease activity index (DAI) score and by histological score. At the conclusion of the experiment, the level of colonic myeloperoxidase (MPO) activity and the serum levels of the cytokines tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and interleukin 10 (IL-10) were measured.
Administration of 3% DSS for 7 days successfully induced acute colitis associated with diarrhea, bloody mucopurulent stool, body weight decreases, and other changes. Colitis severity was significantly ameliorated in the IMQ treatment groups, as determined by hematoxylin-eosin (HE) staining and histopathological scores. Moreover, IMQ significantly reduced the activity of MPO in colonic tissue and the serum levels of inflammatory cytokines, increased colon length and spleen weight, and effectively inhibited microscopic damage to the colon tissue.
IMQ had beneficial effects on DSS-induced ulcerative colitis, supporting its further development and clinical application in ulcerative colitis.
咪喹莫特是一种可调节免疫的Toll样受体7激动剂，可用作免疫佐剂。溃疡性结肠炎与免疫紊乱密切相关。
研究咪喹莫特对葡聚糖硫酸钠（DSS）诱导的结肠炎的治疗效果，并探讨其潜在机制。
C57BL/6J C57小鼠接受3% DSS处理7天以诱导溃疡性结肠炎。每天同时给小鼠腹腔注射地塞米松（DXM，1.5 mg/kg）或咪喹莫特（IMQ，30 mg/kg）。在实验期间，每天监测并记录临床症状、体重、粪便稠度和可见便血情况；通过疾病活动指数（DAI）评分和组织学评分评估结肠炎。实验结束时，测量结肠髓过氧化物酶（MPO）活性水平以及细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素6（IL-6）和白细胞介素10（IL-10）的血清水平。
给予3% DSS 7天成功诱导了与腹泻、血性黏液脓性粪便、体重减轻及其他变化相关的急性结肠炎。苏木精-伊红（HE）染色和组织病理学评分显示，IMQ治疗组的结肠炎严重程度显著改善。此外，IMQ显著降低了结肠组织中MPO的活性以及炎症细胞因子的血清水平，增加了结肠长度和脾脏重量，并有效抑制了结肠组织的微观损伤。
IMQ对DSS诱导的溃疡性结肠炎有有益作用，支持其在溃疡性结肠炎中的进一步研发和临床应用。
