糖基化终末产物对大鼠肾皮质基质金属蛋白酶-2活性的影响

The effect of advanced glycation end products on matrix metalloproteinase-2 activity in rat renal cortex

目的 :观察糖基化终末产物 ( AGEs)和氨基胍 ( AG)对大鼠肾皮质基质金属蛋白酶 - 2( MMP- 2 )活性的影响。方法 :正常雄性 Wistar大鼠 2 3只 ,随机分为 4组 ,AGE-修饰大鼠血清蛋白( AGE- RSP)组 ( n=6)每日尾静脉注射 AGE- RSP,AGEs+ AG组 ( n=6)同时腹腔注射 AG,天然血清组 ( n=6)注射天然大鼠血清蛋白 ,空白对照组 ( n=5 )不施加处理 ,连续注射 4周后 ,用 ELISA法测定肾皮质 AGEs含量 ,酶谱法检测肾皮质 MMP- 2活性。结果 :与天然血清组及空白对照组比较 ,注射 AGE- RSP的大鼠肾皮质 AGEs含量明显增加 ,活性形式的 MMP- 2活性明显降低 ( P<0 .0 5 ) ,而同时注射 AG的大鼠 MMP- 2活性明显增加 ( P<0 .0 5 )。结论 :AGEs能降低大鼠肾皮质MMP- 2活性 ,AG可抑制 AGEs对 MMP- 2活性的影响 ,提示 AGEs通过降低 MMP- 2活性减少肾小球细胞外基质 ( ECM)降解 ,可能是导致 ECM积聚的原因之一。

Objective:To investigate the effect of advanced glycosylated end products (AGEs) and aminoguanidine (AG) on matrix metalloproteinase 2 (MMP 2) activity in rat renal cortex. Methods:Normal rats were given by tail vein injection with either AGE modified rat serum protein(AGE RSP)or AGE RSP followed by intraperitoneal injection of AG(AGEs+AG)or native rat serum protein(native RSP). Normal rats without any treatment were as a control. AGEs amounts in renal cortex were quantified by ELISA and MMP 2 activity was examined by zymography analysis. Results: AGEs amounts of renal cortex was increased markedly and the activity of active form MMP 2 (62KD) reduced significantly in rats neceiving AGE RSP four weeks after treatment as compared with those in rats treated with native RSP or in control. Conclusion: AGEs reduce the activity of MMP 2 in renal cortex and AG inhibits the effect of AGEs on the activity of MMP 2, suggesting that AGEs may induce a decrease in degradation of ECM through inhibition of the MMP 2 activity and result in ECM accumulation.