作　　者： ; ; ; ; ; ;

机构地区： 中山大学生命科学学院生物化学系

出　　处： 《生理学报》 2003年第2期128-134,共7页

摘　　要： 研究观察了重组人白介素 10 (rhIL 10 )对晚期糖基化终产物 (AGE)刺激下离体大鼠胸主动脉血管平滑肌细胞增殖及对SD大鼠血管损伤后新生内膜增殖的影响。体外培养大鼠主动脉血管平滑肌细胞 ,采用MTS/PES法确定血管平滑肌细胞的增殖状态 ;应用流式细胞术测定细胞周期 ;利用 p44 / 42磷酸化抗MAPK抗体的蛋白免疫印迹法测定 p44 / 42MAPK磷酸化蛋白表达。利用大鼠颈动脉血管损伤模型 ,观察rhIL 10对新生内膜增殖的影响。结果显示 :( 1)AGE处理组与对照组相比 ,AGE对血管平滑肌细胞增殖具有明显的刺激作用 (P <0 0 5 )。rhIL 10单独应用对血管平滑肌细胞生长没有影响 (P >0 0 5 )。在AGE刺激下 ,低至 10 0ng/ml的rhIL 10可抑制血管平滑肌细胞的生长 (P <0 0 5 )。( 2 )流式细胞术测定的结果显示 ,rhIL 10可以使AGE作用下的VSMC大部分处于G0 /G1期 ,与对照组相比有明显差异 (P <0 0 1)。 ( 3 )AGE对 p44 / p42MAPK磷酸化蛋白表达有显著的增强作用 ,此作用可被rhIL 10抑制 (P <0 0 0 1)。( 4)大鼠颈动脉损伤后 ,rhIL 10治疗组的动脉血管新生内膜 /中层面积比低于对照组约45 % (P <0 0 1)。表明抗炎细胞因子rhIL The purposes of this study was to determine the effects of recombinant human interleukin-10 (rhIL-10) on proliferation of vascular smooth muscle cells (VSMCs) stimulated by advanced glycation end products (AGE) and neointima hyperplasia after rat carotid arterial injury. Rat aortic VSMCs were cultured and treated with rhIL-10 or AGE respectively, and then co-treated with rhIL-10 and AGE. Proliferation of VSMCs was quantified by colormetric assay. Cell cycle analysis was performed by flow cytomertry. Sprague-Dawley rats were treated with recombinant human IL-10 (rhIL-10) for 3 d after carotid arteries injury. The ratio of neointima to media area at the site of arterial injury was measured 28 d after balloon injury. The p44/42 MAPK activity was evaluated by the immunoblotting technique using anti-p44/42 phospho-MAPK antibody. Compared to control, AGE stimulated VSMCs proliferation. rhIL-10 alone had no effect on VSMCs growth. With AGE stimulation, rhIL-10, at dose as low as 10 ng/ml, inhibited VSMCs growth (P<0 05). The cell number in G 0/G 1 phase of AGE and rhIL-10 co-treatment group was higher than that of AGE treatment alone (P<0 01) by flow cytometry analysis. Compared with the control group of neointima hyperplasia in rats, the ratio of neointima to media area of recombinant human IL-10 group was reduced by 45% (P<0 01). The p44/42 MAPK activity was significantly enhanced by AGE. The AGE effects were opposed by rhIL-10. The anti-inflammatory cytokine rhIL-10 inhibits AGE-induced VSMCs proliferation. Recombinant human IL-10 also inhibited neointima hyperplasia after carotid artery injury in rats. The results suggest the possibility that recombinant human IL-10, as a potential therapeutic approach, prevents neointimal hyperplasia.

关 键 词： 病理学 白介素 肌 平滑 血管 晚期糖基化终产物 新生内膜增殖

领　　域： [生物学]