Requena P, Daddaoua A, Martínez-Plata E, González M, Zarzuelo A, Suárez M D, Sánchez de Medina F, Martínez-Augustin O
Department of Biochemistry and Molecular Biology II, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), School of Pharmacy, University of Granada, Granada, Spain.
Br J Pharmacol. 2008 Jun;154(4):825-32. doi: 10.1038/bjp.2008.138. Epub 2008 Apr 21.
Bovine glycomacropeptide (BGMP) is an inexpensive, non-toxic milk peptide with anti-inflammatory effects in rat experimental colitis but its mechanism of action is unclear. It is also unknown whether BGMP can ameliorate inflammation in proximal regions of the intestine. Our aim was therefore two-fold: first, to determine the anti-inflammatory activity of BGMP in the ileum; second, to characterise its mechanism of action.
We used a model of ileitis induced by trinitrobenzenesulphonic acid in rats. Rats were treated orally with BGMP and its efficacy compared with that of oral 5-aminosalicylic acid or vehicle, starting 2 days before ileitis induction.
BGMP pretreatment (500 mg kg(-1) day(-1)) resulted in marked reduction of inflammatory injury, as assessed by lower extension of necrosis and damage score, myeloperoxidase, alkaline phosphatase, inducible nitric oxide synthase, interleukin 1beta, tumour necrosis factor and interleukin 17. These effects were generally comparable to those of 5-aminosalicylic acid (200 mg kg(-1) day(-1)). Neither compound affected the production of interferon gamma, tumour necrosis factor and interleukin 2 by mesenteric lymph node cells isolated from animals with ileitis. The expression of Foxp3 was increased in ileitis and not reduced significantly by BGMP or aminosalicylate treatment.
These results demonstrate that BGMP has anti-inflammatory activity in the ileum with similar efficacy to 5-aminosalicylic acid. The mechanism of action may involve Th17 and regulatory T cells and perhaps macrophages but probably not Th1 lymphocytes. Patients with Crohn's ileitis may benefit from treatment with BGMP.
牛糖巨肽（BGMP）是一种价格低廉、无毒的乳源肽，在大鼠实验性结肠炎中具有抗炎作用，但其作用机制尚不清楚。BGMP是否能改善肠道近端的炎症也不清楚。因此，我们有两个目标：第一，确定BGMP在回肠中的抗炎活性；第二，阐明其作用机制。
我们使用三硝基苯磺酸诱导大鼠回肠炎模型。在诱导回肠炎前2天开始，给大鼠口服BGMP，并将其疗效与口服5-氨基水杨酸或赋形剂进行比较。
通过坏死范围缩小、损伤评分、髓过氧化物酶、碱性磷酸酶、诱导型一氧化氮合酶、白细胞介素1β、肿瘤坏死因子和白细胞介素17降低来评估，BGMP预处理（500mg kg⁻¹天⁻¹）可显著减轻炎症损伤。这些作用通常与5-氨基水杨酸（200mg kg⁻¹天⁻¹）相当。两种化合物均未影响从患有回肠炎的动物分离的肠系膜淋巴结细胞产生干扰素γ、肿瘤坏死因子和白细胞介素2。回肠炎时Foxp3表达增加，BGMP或氨基水杨酸盐治疗后未显著降低。
这些结果表明，BGMP在回肠中具有抗炎活性，其疗效与5-氨基水杨酸相似。作用机制可能涉及Th17和调节性T细胞，或许还有巨噬细胞，但可能不涉及Th1淋巴细胞。克罗恩病回肠炎患者可能受益于BGMP治疗。
