阿霉素对心肌基质金属蛋白酶和基质金属蛋白酶组织抑制因子表达的影响  

Effect of Adriamycin on the Expressions of MMPs and TIMP- 1 in Myocardium of Rats

作　　者：杨鑫[1] 宋怡[2] 张敏[3] 思永玉[4] 

机构地区：[1]云南省第二人民医院麻醉科,云南昆明650021 [2]昆明医学院第一附属医院心外科,云南昆明650032 [3]昆明医学院第一附属医院心内科,云南昆明650032 [4]昆明医学院第二附属医院麻醉科,云南昆明650101

出　　处：《昆明医学院学报》2009年第2期5-8,共4页Journal of Kunming Medical College

基　　金：国家自然科学基金资助项目(30560036)

摘　　要：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Westernblotting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-1mRNA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JNKMAPK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.p38MAPK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.

关 键 词：阿霉素 基质金属蛋白酶 基质金属蛋白酶组织抑制因子 P38 MAPK激酶 

分 类 号：R541.6[医药卫生—心血管疾病]