阻断CD40-CD40配体系统对动脉粥样硬化的影响

目的探讨阻断CD40-CD40配体系统对动脉粥样硬化的影响。方法18只载脂蛋白E基因敲除小鼠随机分为阳性对照组(n=10)和抗CD40配体抗体组(n=8),并以近交系C57BL/6小鼠作为正常对照。测定血脂、可溶性血管细胞粘附分子1和可溶性细胞间粘附分子1浓度。观察主动脉组织病理形态学改变,免疫组织化学法测定斑块部位巨噬细胞、平滑肌细胞和CD4 T细胞百分率。Western杂交分析测定基质金属蛋白酶9的蛋白表达。结果抗CD40配体抗体治疗可明显降低可溶性血管细胞粘附分子1和可溶性细胞间粘附分子1浓度(P<0.01),对血脂无明显影响(P>0.05);可减轻动脉粥样硬化病变,减少斑块部位巨噬细胞和CD4 T细胞,增加平滑肌细胞数量(P<0.05),降低基质金属蛋白酶9的表达(P<0.01)。结论阻断CD40-CD40配体系统可使血清可溶性粘附分子浓度下降,抑制炎症反应,从而减轻动脉粥样硬化病变,对血脂无影响。

Effects of Inhibition of CD40-CD40 Ligand System on Atherosclerosis

Aim To evaluate the effects of inhibition of CD40-CD40 ligand system on development of atherosclerosis and the stability of lesions. Methods Eighteen male apolipoprotein E gene knockout mice were divided into positive control group(n=10) and anti-CD40 ligand antibody group(n=8).Serum lipids,soluble vascular cell adhesion molecule-1 and soluble intercellular adhension molecule-1 were deteced.The aortas were taken for histomorphometry observation.The positive percentage of macrophage cells,smooth muscle cells and CD4~ T cells were determined by immunohistochemistry,and the expression of matrix metalloproteinase-9 were mesurated by Western blotting. Results Anti-CD40 ligand treatment could lower the levels of serum soluble vascular cell adhesion molecule-1 and soluble intercellular adhension molecule-1(P<0.01).It had no impact on serum lipids(P>0.05).Compared with positive control group,anti-CD40 ligand group showed a reduction in plaque area,plaque/intima size ratio,vascular thickness(P<0.05).Inhibition CD40-CD40 ligand also could reduce the amount of macrophage cells and CD4~ T cells,increase the amount of smooth muscle cells(P<0.05).The expression of matrix metalloproteinase-9 decreased in anti-CD40 ligand antibody group(P<0.01). Conclusions Inhibition of CD40-CD40 ligand could decrease vascular inflammation,prevent development of atherosclerosis.It had no impact on serum lipids.