Effect of a high dose of glucosamine on systemic and tissue inflammation in an experimental model of atherosclerosis aggravated by chronic arthritis
Effect of a high dose of glucosamine on systemic and tissue inflammation in an experimental model of atherosclerosis aggravated by chronic arthritis
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DOI：
10.1152/ajpheart.00142.2009
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发表时间：
2009-07-01
影响因子：
4.8
通讯作者：
Herrero-Beaumont, Gabriel
中科院分区：
文献类型：
--
作者：
Largo, Raquel;Jose Martinez-Calatrava, Maria;Herrero-Beaumont, Gabriel
[10]李文亮，李文亮.高剂量氨基葡萄糖对慢性关节炎加重动脉粥样硬化实验模型全身和组织炎症的影响。Am J Physiol Heart Circ Physiol 297：H268-H276，2009.首次发表于2009年5月1日; doi：10.1152/ajpheart.00142.2009。硫酸氨基葡萄糖（GS）是一种具有抗炎和免疫调节特性的糖胺聚糖。在这里，我们着手探讨GS管理的影响，全身和局部炎症标记物的动脉粥样硬化加重慢性关节炎的兔。在股动脉中产生内皮损伤后，通过维持高血脂饮食诱导家兔动脉粥样硬化。同时，通过在先前免疫的兔中重复关节内注射卵清蛋白在这些动物中诱导慢性关节炎。这些家兔中的一组用口服GS进行免疫治疗（500 mg.kg（-1）.day（-1）），当动物被杀死时，提取血清并分离外周血单核细胞（PBMC）。此外，在基因表达研究和组织学上检查了股动脉、胸主动脉和滑膜。GS给药降低了C反应蛋白和白细胞介素-6的循环水平。GS还降低PBMC中核因子-κ B活化，并下调这些细胞中的CCL 2（单核细胞趋化蛋白）和环氧合酶-2基因的表达。GS治疗后股壁病变较轻，这反映在内膜-中膜增厚率和无主动脉病变。事实上，GS也减弱了滑膜组织中的组织学病变。在慢性关节炎和动脉粥样硬化的组合兔模型中，口服给药GS减少外周血中的炎症标志物，以及股骨和滑膜病变。GS还可预防炎症相关的主动脉病变的发展。这些结果表明GS具有动脉粥样硬化保护作用。
Largo R, Martinez-Calatrava MJ, Sanchez-Pernaute O, Marcos ME, Moreno-Rubio J, Aparicio C, Egido J, Herrero-Beaumont G. Effect of a high dose of glucosamine on systemic and tissue inflammation in an experimental model of atherosclerosis aggravated by chronic arthritis. Am J Physiol Heart Circ Physiol 297: H268-H276, 2009. First published May 1, 2009; doi: 10.1152/ajpheart.00142.2009.-Glucosamine sulfate (GS) is a glycosaminoglycan with anti-inflammatory and immunoregulatory properties. Here we set out to explore the effect of GS administration on markers of systemic and local inflammation in rabbits with atherosclerosis aggravated by chronic arthritis. Atherosclerosis was induced in rabbits by maintaining them on a hyperlipidemic diet after producing an endothelial lesion in the femoral arteries. Simultaneously, chronic arthritis was induced in these animals by repeated intra-articular injections of ovalbumin in previously immunized rabbits. A group of these rabbits was treated prophylactically with oral GS (500 mg.kg(-1).day(-1)), and, when the animals were killed, serum was extracted and peripheral blood mononuclear cells (PBMC) were isolated. Furthermore, the femoral arteries, thoracic aorta, and synovial membranes were examined in gene expression studies and histologically. GS administration reduced circulating levels of the C-reactive protein and of interleukin-6. GS also lowered nuclear factor-kappa B activation in PBMC, and it downregulated the expression of both the CCL2 (monocyte chemoattractant protein) and cyclooxygenase-2 genes in these cells. Lesions at the femoral wall were milder after GS treatment, as reflected by the intimal-to-media thickened ratio and the absence of aortic lesions. Indeed, GS also attenuated the histological lesions in synovial tissue. In a combined rabbit model of chronic arthritis and atherosclerosis, orally administered GS reduced the markers of inflammation in peripheral blood, as well as the femoral and synovial membrane lesions. GS also prevented the development of inflammation-associated aortic lesions. These results suggest an atheroprotective effect of GS.