Department of Pharmacology and Therapeutics of the State University of Maringá, Maringá, PR, Brazil.
Department of Biochemistry of the State University of Maringá, Maringá, PR, Brazil.
Inflammation. 2017 Apr;40(2):717-724. doi: 10.1007/s10753-016-0497-x.
Statins are hypocholesterolemic drugs that are prescribed for patients with an increased risk of cardiovascular and cerebrovascular complications. Ezetimibe has an atheroprotective activity through inhibition of the expression of vascular adhesion molecule-I and vascular CD14, a marker of the infiltration of mononuclear leukocytes. Ezetimibe reduces the amount of chemoattractant protein-1 that is available for monocytes and macrophages and alters the activity of nuclear factor κB in leukocytes. The mechanisms of action of statins complement those of ezetimibe. Previous studies have demonstrated that the combination of statins and ezetimibe has beneficial effects, including antiinflammatory activity. The present study evaluated the effects of monotherapy with ezetimibe and simvastatin compared with ezetimibe + simvastatin combined on the evolution of the inflammatory response in a rat model of Complete Freund's Adjuvant-induced arthritis. The animals were treated with 10 mg/kg ezetimibe, 40 mg/kg simvastatin, or 10 mg/kg ezetimibe + 40 mg/kg simvastatin for 1, 7, 14, or 28 days. We analyzed leukocyte rolling behavior, leukocyte adhesion to the endothelium, the number of leukocytes that were recruited to the knee joint cavity, and the concentration of cytokines that are involved in the inflammatory response. The data were analyzed using paired t tests or analysis of variance followed by Bonferroni post hoc test. The treatments reduced leukocyte rolling behavior and leukocyte adhesion. The monotherapies did not change the number of leukocytes that were recruited to the knee joint cavity, whereas the ezetimibe + simvastatin combination significantly reduced this parameter. The treatments reduced the levels of proinflammatory cytokines and increased the levels of the antiinflammatory cytokine IL-10, indicating antiinflammatory properties of these drugs in this experimental model of inflammation.
他汀类药物是降胆固醇药物，用于治疗心血管和脑血管并发症风险增加的患者。依折麦布通过抑制血管黏附分子-1 和血管 CD14（单核白细胞浸润的标志物）的表达发挥抗动脉粥样硬化作用。依折麦布减少单核细胞和巨噬细胞可用的趋化蛋白-1 量，并改变白细胞中核因子 κB 的活性。他汀类药物的作用机制补充了依折麦布的作用机制。先前的研究表明，他汀类药物和依折麦布联合具有有益作用，包括抗炎活性。本研究评估了依折麦布和辛伐他汀单药治疗与依折麦布+辛伐他汀联合治疗对完全弗氏佐剂诱导关节炎大鼠模型中炎症反应进展的影响。动物接受 10mg/kg 依折麦布、40mg/kg 辛伐他汀或 10mg/kg 依折麦布+40mg/kg 辛伐他汀治疗 1、7、14 或 28 天。我们分析了白细胞滚动行为、白细胞与内皮的黏附、招募到膝关节腔的白细胞数量以及参与炎症反应的细胞因子浓度。使用配对 t 检验或方差分析，然后进行 Bonferroni 事后检验分析数据。这些治疗方法降低了白细胞滚动行为和白细胞黏附。单药治疗并未改变招募到膝关节腔的白细胞数量，而依折麦布+辛伐他汀联合治疗显著降低了这一参数。这些治疗方法降低了促炎细胞因子的水平，增加了抗炎细胞因子 IL-10 的水平，表明这些药物在这种炎症实验模型中具有抗炎特性。
