目的研究阿霉素对大鼠心肌的基质金属蛋白酶(MMPs)和基质金属蛋白酶组织抑制因子(TIMP-1)表达的影响.方法采用RT—PCR测定mRNA水平,采用Western blotting测定蛋白质水平及蛋白质磷酸化.结果阿霉素处理导致大鼠心肌组织MMP-2、MMP-9、TIMP-1 mRNA和蛋白质水平均升高.阿霉素处理还诱导p38MAPK激酶磷酸化水平增加,但不影响Erk1/2和JNK MAPK激酶磷酸化水平.结论在阿霉素介导的心衰发展过程中,胞外基质的降解和累积同时发生.p38 MAPK激酶可能参与了阿霉素诱导的心肌毒性作用.
Objective To study the effect of adriamycin on the expressions of MMPs and TIMP-1 in myocardium of rats. Methods The mRNA levels of genes were detected by RT-PCR. The protein levels and phosphorylation were determined by Western blotting. Results Adriamycin treatment resulted in an increase in both mRNA and protein levels of MMP-2, MMP-9 and TIMP-1 in myocardium. Adriamycin treatment promoted the phosporylation of p38 MAPK, rather than Erkl/2 and JNK MAPKs. Conclusion The degradation and accumulation of extracellular matrix probably occurred simultantly, p38 MAPK is involved in adriamycin-induced cardiotoxicity.