糖基化终产物对平滑肌细胞增殖及纤溶酶原激活物抑制剂1基因表达的影响
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Effect of Advanced Glycation End Product on Cellular Proliferation and Expression of Plasminogen Activator Inhibitor-1 in Rat Vascular Smooth Muscle Cell
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    摘要:

    目的探讨糖基化终产物对大鼠平滑肌细胞增殖以及纤溶酶原激活物抑制剂1基因表达的影响。方法体外分离培养大鼠平滑肌细胞,以不同浓度(50、100、200和400mg/L)糖基化终产物作用于平滑肌细胞不同时间(0、4、8、16、24、48、72和96h),MTT法观察糖基化终产物对平滑肌细胞增殖的影响,逆转录聚合酶链反应测定纤溶酶原激活物抑制剂1基因的表达。结果不同浓度的糖基化终产物作用8h均对平滑肌细胞增殖无影响,以后各时间点不同浓度的糖基化终产物均导致平滑肌细胞增殖,与对照组比较差异有显著性(p<0.05)。糖基化终产物作用不同时间均可使平滑肌细胞表达纤溶酶原激活物抑制剂1基因水平升高,且随着浓度升高而增加(分别为0.85±0.05、0.97±0.05、1.08±0.12和1.41±0.05),与对照组(0.80±0.03)比较差异有显著性(p<0.05)。结论糖基化终产物诱导血管平滑肌细胞增殖并增加纤溶酶原激活物抑制剂1基因表达是糖尿病患者易患动脉粥样硬化的可能原因。

    Abstract:

    Aim To investigate the effects of advanced glycation end product(AGE)on cellular proliferation and expression of plasminogen activator inhibitor-1(PAI-1)in cultured rat aortic vascular smooth muscle cell(VSMC).Methods Primary cultures of smooth muscle cell from rat aorta were exposed to AGE of different times and different concentrations.3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)assay was adopted for the quantification of the cell proliferation ratio and PAI-1 expression was determined by reverse-transcription polymerase chain reaction(RT-PCR).Results Cell proliferation in different AGE concentration medium was greater than that in nonglycated BSA medium(p<0.05),except for 8 hours.After intervention of AGE,plasminogen activator inhibitor-1 mRNA was increased markedly(p<0.001)in a time-related manner.The expression of plasminogen activator inhibitor-1 mRNA was upregulated in a dose-related manner(0.85±0.05,0.97±0.05,1.08±0.12,1.41±0.05),in comparison with that in control group(0.80±0.03,p<0.05).Conclusion AGE induced proliferation and the expression of PAI-1 mRNA in VSMC.This may be involved in the pathogenesis of atherosclerosis in patients with diabetes mellitus.

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李爱华,袁晓晨,高阳.糖基化终产物对平滑肌细胞增殖及纤溶酶原激活物抑制剂1基因表达的影响[J].中国动脉硬化杂志,2007,15(1):43~46.

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  • 收稿日期:2006-07-19
  • 最后修改日期:2006-11-20
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