MMP-2、MMP-9在大鼠肾缺血再灌注损伤早期的表达及意义

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。

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

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 increase 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.