p38MAPK对大鼠肾缺血再灌注损伤早期MMP-9表达的调控

Early expression of p38MAPK and MMP-9 and their significance in renal ischemia-reperfusion injury

目的探讨p38MAPK对大鼠肾缺血再灌注后MMP-9表达的调控情况及它们在肾缺血再灌注损伤中的作用。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,测定各组实验大鼠血清肌酐水平的变化,应用免疫组化二步法检测p38MAPK、MMP-9表达的变化。结果与假手术组比较,缺血再灌注各组血清肌酐水平升高,缺血45min再灌注,24h达高峰(P<0.01)。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、24h及72h呈阳性表达,在24h达高峰(P<0.01);p38MAPK蛋白在假手术组呈少量散在表达或不表达,缺血45 min,再灌注6、12h及24 h呈阳性表达,12h达高峰(P<0.01)。p38MAPK,MMP-9蛋白的表达与血清肌酐水平的变化呈显著正相关。结论肾缺血再灌注可激活p38MAPK,活化的p38MAPK可以上调MMP-9蛋白的表达,可能促进了肾缺血再灌注损伤的发生和发展。

Objective To investigate the influence of p38MAPK on the expression of matrix metalloproteinase-9（MMP-9） after renal ischemia-reperfusion injury and to study their effect on renal ischemia-reperfusion injury. Methods Renal ischemia-reperfu- sion injury models of rat were established. To measuring blood creatinine（Cr） levels for assessing kidney dysfunction. Two-step immunohistochemical methods were used to dedect the changes of expression of p38MAPK,MMP-9. Results Cr levels was obviously increased compared with that of the sham group, and peaked at 24h of reperfusion （P〈0.01）. The 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〈0.01）, p38MAPK mainly located at the same areas, peaked at 12h of reperfusion and was negatively/weakly expressed in the sham group （P〈0.01）. And the high expression of p38MAPK and MMP-9 were positively correlated with Cr. Conclusion The activation of p38MAPK may increase the levels of MMP-9 ,and p38MAPK,MMP-9 may play important roles in early renal ischemia-reperfusion injury and its severity.