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重组人白介素10抑制晚期糖基化终产物诱导的大鼠血管平滑肌细胞和血管新生内膜的增殖

欧阳平, 彭立胜, 杨红, 彭文烈, 吴文言, 徐安龙

中山大学生命科学学院生物化学系，广州510275

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p44/42 MAPK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. 05) o rhIL 1 0单独应用对血管平滑肌细胞生长没有影响(P>0.05)。在AGE刺激下，低至100 ng/ ml的rhIL 10可抑制血管平滑肌细胞的生长(P < 0. 05) o (2)流式细胞术测定的结果显示，rhIL 10可以使AGE作用下的VS MC大部分处于Go/ G,与对照组相比有明显差异(P<0.01) o (3) AGE对p44/ p42 MAPK磷酸化蛋白表达有显著的增强作用，此作用
可被:hIL 10抑制(P<0.001) o (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0.01)。表明抗炎细胞因子rhIL 10可抑制AGE诱导的大鼠血管平滑肌细胞增殖和血管新生内膜的增殖。

关键词： 病理学; 白介素10; 肌; 平滑; 血管; 晚期糖基化终产物; 新生内膜增殖

Recombinant human interleukirr 10 inhibits proliferation of vascular smooth muscle cells sti mutated场advanced glycation end products and neoirnti ma hyperplasia after carotid in3 ury in the rat

OU YANG Ping, PE NG Li-Sheng, Yang Hong, PENG Weir Lie, WU Wen Yan, XU Air Long

Department of Biochemistry，School of Life Science，Sun Yat-sen University，Guangzhou 510275，China

Abstract

The purposes of this study was to determine the effects of recombinant human interleukirrl0(rhIL 10) on proliferation of vascular smooth muscle cells(VS MCs) stimulated by advanced glycation end products(AGE) and neointima by-
perplasia after rat carotid arterial injury .Rat aortic VS MCs 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 anti7p44/42 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 VS MCs growth(P(0. 05).The cell number in Go/ G,
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 anti7inflammatory 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.

Key words: pathology;interleukin-10;muscle;smooth;vascular;;

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引用本文：

欧阳平, 彭立胜, 杨红, 彭文烈, 吴文言, 徐安龙. 重组人白介素10抑制晚期糖基化终产物诱导的大鼠血管平滑肌细胞和血管新生内膜的增殖[J]. 生理学报 2003; 55 (2): .

OU YANG Ping, PE NG Li-Sheng, Yang Hong, PENG Weir Lie, WU Wen Yan, XU Air Long. Recombinant human interleukirr 10 inhibits proliferation of vascular smooth muscle cells sti mutated场advanced glycation end products and neoirnti ma hyperplasia after carotid in3 ury in the rat. Acta Physiol Sin 2003; 55 (2): (in Chinese with English abstract).