Department of Physiology and Pharmacology 'Vittorio Erspamer', University SAPIENZA of Rome, P le Aldo Moro 5, 00185 Rome, Italy.
J Neuroinflammation. 2012 Dec 23;9:277. doi: 10.1186/1742-2094-9-277.
Intestinal inflammation is partly driven by enteroglial-derived S100B protein. The antiprotozoal drug pentamidine directly blocks S100B activity. We aimed to investigate the effect of pentamidine on intestinal inflammation using an animal model of dextran sodium sulphate (DSS)-induced acute colitis.
Mice were divided into: control group, colitis group (4% DSS for four days) and two pentamidine-treated colitis groups (0.8 mg/kg and 4 mg/kg). Anti-inflammatory effect of pentamidine was assessed in colonic tissue by evaluating the disease activity index and the severity of histological changes. Colonic tissue were also used to evaluate cyclooxigenase-2, inducible nitric oxide synthase, S100B, glial fibrillary acidic protein, phosphorylated-p38 MAPkinase, p50, p65 protein expression, malondyaldheyde production, mieloperoxidase activity, and macrophage infiltration. Nitric oxide, prostaglandin E2, interleukin-1 beta, tumor necrosis factor alpha, and S100B levels were detected in plasma samples. Parallel measurements were performed in vitro on dissected mucosa and longitudinal muscle myenteric plexus (LMMP) preparations after challenge with LPS + DSS or exogenous S100B protein in the presence or absence of pentamidine.
Pentamidine treatment significantly ameliorated the severity of acute colitis in mice, as showed by macroscopic evaluation and histological/biochemical assays in colonic tissues and in plasma. Pentamidine effect on inflammatory mediators was almost completely abrogated in dissected mucosa but not in LMMP.
Pentamidine exerts a marked anti-inflammatory effect in a mice model of acute colitis, likely targeting S100B activity. Pentamidine might be an innovative molecule to broaden pharmacological tools against colitis.
肠道炎症部分由肠胶质衍生的 S100B 蛋白驱动。抗原生动物药物戊脒直接阻断 S100B 活性。我们旨在使用葡聚糖硫酸钠（DSS）诱导的急性结肠炎动物模型研究戊脒对肠道炎症的影响。
将小鼠分为：对照组、结肠炎组（4% DSS 四天）和两个戊脒治疗结肠炎组（0.8mg/kg 和 4mg/kg）。通过评估疾病活动指数和组织学变化的严重程度，评估戊脒对结肠组织的抗炎作用。还使用结肠组织评估环氧化酶-2、诱导型一氧化氮合酶、S100B、胶质纤维酸性蛋白、磷酸化-p38MAPkinase、p50、p65 蛋白表达、丙二醛产生、髓过氧化物酶活性和巨噬细胞浸润。检测血浆样本中的一氧化氮、前列腺素 E2、白细胞介素-1β、肿瘤坏死因子-α和 S100B 水平。在 LPS+DSS 或外源性 S100B 蛋白刺激下，在存在或不存在戊脒的情况下，对分离的粘膜和纵向肌肌间神经丛（LMMP）进行体外平行测量。
戊脒治疗显著改善了小鼠急性结肠炎的严重程度，如在结肠组织和血浆中的宏观评估和组织学/生化测定中所示。戊脒对炎性介质的作用在分离的粘膜中几乎完全被消除，但在 LMMP 中没有被消除。
戊脒在急性结肠炎小鼠模型中表现出明显的抗炎作用，可能靶向 S100B 活性。戊脒可能是一种创新的分子，可以扩大治疗结肠炎的药理学工具。
