糖基化终末产物对大鼠肾皮质PAI-1表达和活性的影响

Effects of advanced glycation end products on expression and activity of PAI-1 in rat renal cortex

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。

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 RTPCR. 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. 584-0.11, P〈0.05）. At the same time, renal ECM controhents increased in AGEs group. All the changes were attenuated in AG treatment rats. Conclusions AGEs up-regulate PAId expression and decrease PA activity, which may be one of mechanisms of ECM accumulation in diabetic nephropathy development.