Herrero-Beaumont G, Marcos M E, Sánchez-Pernaute O, Granados R, Ortega L, Montell E, Vergés J, Egido J, Largo R
Joint and Bone Research Unit and Vascular Research Laboratory, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
Br J Pharmacol. 2008 Jun;154(4):843-51. doi: 10.1038/bjp.2008.113. Epub 2008 Apr 21.
Among the agents employed to manage osteoarthritis, chondroitin sulphate (CS) is a natural glycosaminoglycan with an anti-inflammatory effect on joint cells. CS might also influence the inflammatory component of atherosclerosis. Our aim was to examine the effect of CS administration on vascular injury and on markers of systemic inflammation in a rabbit model of atherosclerosis aggravated by systemic inflammation provoked by chronic antigen-induced arthritis.
Atherosclerosis was induced in rabbits by maintaining them on a hyperlipidaemic diet after producing an endothelial lesion in the femoral arteries. Simultaneously, chronic arthritis was induced in these animals by repeated intraarticular injections of ovalbumin in previously immunized rabbits. A group of these rabbits were treated prophylactically with CS (100 mg kg(-1)day(-1)) and when the animals were killed, serum and peripheral blood mononuclear cells (PBMC) were isolated. Furthermore, femoral arteries and thoracic aorta were used for gene expression studies and histological examination.
CS administration reduced the concentration of the proinflammatory molecules C-reactive protein and IL-6 in serum. Likewise, CS inhibited the expression of CCL2/monocyte chemoattractant protein (MCP)-1 and cyclooxygenase (COX)-2 in PBMC, and reduced the nuclear translocation of nuclear factor-kappaB. In the femoral lesion, CS also diminished the expression of CCL2 and COX-2, as well as the ratio of the intima/media thickness. Moreover, CS decreased the percentage of rabbits with atherosclerosis and chronic arthritis that developed vascular lesions in the aorta.
These findings suggest that CS treatment may to some extent impede the progression of atherosclerosis.
在用于治疗骨关节炎的药物中，硫酸软骨素（CS）是一种对关节细胞具有抗炎作用的天然糖胺聚糖。CS 可能还会影响动脉粥样硬化的炎症成分。我们的目的是在慢性抗原诱导性关节炎引发的全身炎症加重的动脉粥样硬化兔模型中，研究给予 CS 对血管损伤和全身炎症标志物的影响。
在兔股动脉造成内皮损伤后，通过高脂饮食诱导兔发生动脉粥样硬化。同时，对这些动物通过在先前免疫的兔中反复关节内注射卵清蛋白诱导慢性关节炎。其中一组兔预防性给予 CS（100 mg·kg⁻¹·天⁻¹），处死动物时，分离血清和外周血单核细胞（PBMC）。此外，取股动脉和胸主动脉用于基因表达研究和组织学检查。
给予 CS 可降低血清中促炎分子 C 反应蛋白和白细胞介素-6 的浓度。同样，CS 抑制 PBMC 中 CCL2/单核细胞趋化蛋白（MCP）-1 和环氧化酶（COX）-2 的表达，并减少核因子-κB 的核转位。在股动脉病变中，CS 还减少了 CCL2 和 COX-2 的表达以及内膜/中膜厚度比值。此外，CS 降低了发生主动脉血管病变的动脉粥样硬化和慢性关节炎兔的百分比。
这些发现表明 CS 治疗可能在一定程度上阻碍动脉粥样硬化的进展。
