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动脉去内皮损伤后降脂药物对生长因子作用影响的分子机制(英文)
Molecular basis for the effect of lipid lowering drugs on growth factors after de-endothelialization
【摘要】 目的 研究血管成型术后降脂药物抑制动脉再狭窄形成的作用及其作用机制。方法 应用球囊导管对家兔主动脉 ,髂及股动脉造成去内膜损伤以观察使用降血脂药物simvastatin +gemfibrozil或单一使用simvastatin 6星期后对内膜生长因子包括血小板源生长因子 (PDGF B) ,转移生长因子 1(TGF 1) ,碱性纤维母细胞生长因子 (bFGF)以及血清总胆固醇 (TC)和甘油三脂 (TG)的影响。结果 给予降血脂药 6周的两组家兔 ,虽同时摄入高胆固醇但血清TC和TG(simvastatin +gemfibrozil组 )水平仅有轻度或中度升高。此外 ,还观察到血清TC水平和内膜 /中膜比值呈正相关 (r=0 5 873,P <0 0 5 )。免疫组化染色及RT PCR扩增检测均显示simvastastin +gemfibrozil可抑制去内皮手术后内膜PDGF B的释放。RT PCR还显示两组治疗组新生内膜内均有TGF 1表达增加。但手术组及治疗组动物受损伤动脉壁的平滑肌细胞内bFGFmRNA无明显改变。结论 降脂药simvastatin和gemfibrozil除具有降血脂功能外 ,还影响去内膜手术损伤后动脉新生内膜内PDGF B和TGF 1的释放。
【Abstract】 To study the mechanism and effect of lipid lowering drugs in arresting the development of arterial restenosis after angioplasty Methods De endothelialization injury of rabbit aortae, common iliac and femoral arteries using balloon angioplasty and the expression of growth factors such as platelet derived growth factor B (PDGF B), transforming growth factor β 1 (TGFβ 1), and fibroblast growth factos (bFGF) were investigated Total serum cholesterol (TC) and triglycerides (TG) were analyzed during and after the treatment using either simvastatin combined with gemfibrozil or simvastatin alone for 6 weeks Results Serum total cholesterol and triglycerides were only slightly to moderately increased after high cholesterol ration intake lasting for 6 weeks in rabbits of two therapeutic groups (simvastatin plus gemfibrozil or only simvastatin) A positive correlation was found between TC and intimal/medial ratio ( r =0 5873, P <0 05) PDGF B detected by immuno histochemistry and RT PCR analysis showed that the release of PDGF B was inhibited by simvastatin and gemfibrozil after de endothelialization RT PCR analysis showed that TGFβ 1 was increased in the neointima in two treatment groups but no definite change was seen in the mRNA of bFGF in the smooth muscle cell (SMC) of the balloon injured arteries even under lipid lowering drug treatment Conclusion In addition to the lipid lowering effect, both simvastatin and gemfibrozil also influence the release of PDGF Band TGF 1 in the neointima after de endothelialization
【Key words】 arterial injury · restenosis · lipid lowering drugs · cell mediators;
- 【文献出处】 Chinese Medical Journal ,中华医学杂志(英文版) , 编辑部邮箱 ,2001年09期
- 【分类号】R965
- 【被引频次】6
- 【下载频次】43