【摘要】 目的观察糖基化终末产物(AGEs)对大鼠肾皮质纤溶酶原激活物抑制物-1(PAI-1)表达和活性的影响。方法大鼠尾静脉注射AGE修饰大鼠血清蛋白(AGEs)6周,其中部分大鼠同时腹腔注射AGE形成抑制剂氨基胍(AG),以注射天然大鼠血清蛋白(RSP)和正常大鼠(Con)作为对照。免疫组织化学、Western blot、RT-PCR检测PAI-1表达水平,酶谱法分析纤溶酶原激活物(PA)活性,PAS染色评估细胞外基质(ECM)含量。结果与Con组及RSP组比较,AGEs组大鼠肾皮质ECM含量、PAI-1蛋白及mRNA表达水平均明显增高,PA活性明显降低(PAI-1 mRNAP<0.01,其余P<0.05),而同时注射AG的大鼠上述变化明显减轻。结论AGEs上调大鼠肾皮质PAI-1的表达,抑制PA活性,可能是糖尿病肾病ECM积聚的原因之一。更多还原

【Abstract】 Objective To investigate the effects of advanced glycation end products(AGEs) on plasminogen activator inhibitor-1(PAI-1) expression and activity in rat renal cortex.Methods AGE-modified rat serum protein was given to rats alone(AGEs group) or combined with AGEs inhibitor aminoguanidine(AG group).Nothing(control) and rat serum protein(RSP group)were given to rats as controls.PAI-1 expression was analyzed by immunohistochemistry,Western blot and RT-PCR.Zymogram was used to analyze plasminogen activator(PA) activity.PAS stain was used to evaluate extracellular matrix(ECM) contents.Results The expression of PAI-1 in renal cortex was up-regulated and the PA activity was decreased in AGEs-treated rat,as compared with those in control and RSP group(PAI-1 mRNA: control 0.15±0.02,RSP 0.16±0.03 vs AGEs 0.28±0.05,P<0.01;PAI-1 protein: control 0.82±0.28,RSP 0.96±0.30 vs AGEs 1.58±0.41,P<0.05;PA activity: control 1.03±0.21,RSP 0.98±0.25 vs AGEs 0.58±0.11,P<0.05).At the same time,renal ECM controltents increased in AGEs group.All the changes were attenuated in AG treatment rats.Conclusions AGEs up-regulate PAI-1 expression and decrease PA activity,which may be one of mechanisms of ECM accumulation in diabetic nephropathy development.更多还原