MMP-2、MMP-9在大鼠肾缺血再灌注损伤早期的表达及意义

Early expressions of MMP-2 and MMP-9 and their significance in renal ischemia-reperfusion injury

目的探讨大鼠肾缺血再灌注后肾组织中MMP-2、MMP-9的表达及在肾缺血再灌注损伤中的作用机制。方法48只健康雄性SD大鼠,分组建立大鼠肾缺血再灌注损伤模型,应用免疫组化二步法检测MMP-2、MMP-9表达的变化,测定肾组织髓过氧化物酶(MPO)活性及血清肌酐(Scr)水平,以反映中性粒细胞浸润及肾功能损害的程度变化。结果MMP-2、MMP-9蛋白在假手术组呈少量散在表达或不表达,缺血45min再灌注6h有少量表达,再灌注12、24、72h呈阳性表达,以24h达高峰(P<0.05),多表达在皮质深层近曲小管及髓质区。与假手术组比较,缺血再灌注各组Scr水平和MPO的活性升高,且随再灌注时间延长而进一步升高,24h达高峰(P<0.01)。MMP-2和MMP-9蛋白的表达变化与Scr水平呈显著性正相关关系(r分别为0.763和0.874,P<0.01);与MPO活性也呈显著性正相关关系(r分别为0.752和0.693,P<0.01)。结论肾缺血再灌注后肾组织中MMP-2、MMP-9表达增加,提示MMP-2、MMP-9可能与早期肾缺血再灌注后损伤及加重有关。

Objective To investigate the ealy expressions of matrix metalloproteinase-2（MMP-2） and matrix metalloproteinase-9 （MMP-9） after renal ischemia-reperfusion injury and to study their effect and machenism on renal ischemia-reperfusion injury. Methods Renal ischemia-reperfusion injury models of rat were established. Two-step immunohistochemical methods were used to dedect the changes of expression of MMP-2,MMP-9. To Measure myeloperxide（MPO） activity and blood creatinine（Cr） levels for assessing neutrophil influx and kidney dysfunction. Results MMP-2 and MMP-9 mainly expressed in deep layer renal proximal convoluted tubules and medullary substance, gradually upregulated with duration of ischemia-reperfusion, and peaked at 24h of reperfusion and were negatively/weakly expressed in the sham group（P〈0.05）. The blood creatinine（Cr） levels and the myeloperxide（MPO） activity were obviously increased compared with those of the group sham,and peaked at 24h of reperfusion（P〈0.01）. And the high expressions of MMP-2 and MMP-9 were positively correlated with the blood creatinine（r=0. 763,P〈0.01 ;r =0. 874,P〈0.01 ,respectively） ,and the MPO activity（r=0. 752,P〈0.01;r=0. 693,P〈0.01 ,respectively）. Conclusion The in- crease of MMP-2,MMP-9 expression suggests that MMP-2, MMP-9 may play important roles in early renal ischemia-reperfusion injury and its severity.