基质金属蛋白酶在阿霉素心肌病左室重构中的表达与意义

目的:研究基质金属蛋白酶(MMPs)及金属蛋白酶组织抑制因子(TIMPs)在阿霉素心肌病(ADR DCM)大鼠左室心肌中的表达与意义。方法:雄性Wistar大鼠分两组:正常对照组(n=10)和ADR DCM组(n =25)。ADR DCM模型建立方法:阿霉素2.5mg/kg,尾静脉注射,每周1次,连续10周。12周时进行超声检测 评价其心功能,硫代巴比妥酸法检测丙二醛(MDA)含量,逆转录 聚合酶链反应、Western印迹分析检测MMP 2、 MMP 9及TIMP 1的表达。结果:ADR DCM组大鼠死亡率40%,左室舒张末期内径及收缩末期内径增加,左室 短轴缩短率明显下降,MDA含量增加(P<0.01)。ADR DCM组大鼠左室心肌MMP 2、MMP 9mRNA及蛋白 水平表达较正常对照组明显升高(P<0.01),而TIMP 1的表达在两组间均无统计学意义(P>0.05)。结论: ADR DCM左室心肌MMPs表达上调,MMPs可能参与ADR DCM左室重构和心力衰竭的发生发展。

Expression of matrix metalloproteinases in the development of adriamycin -induced dilated cardiomyopathy

Objective:To investigate the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the development of adriamycin-induced dilated cardiomyopathy(ADR-DCM). Method:Twenty-five adult male Wistar rats were injected with adriamycin at a dose of 2.5 mg/kg intravenously once a week for 10 weeks, ten control rats were injected with saline intravenously. Echocardiographic measurements were obtained at 12 weeks after treatment. Finally, LV tissue samples were collected. The malondialdehyde(MDA) was investigated by the methods of TBA; MMP-2, MMP-9 and tissue inhibitors of metalloproteinase-1 (TIMP-1) were measured by RT-PCR and Western blot. Result:In rats treated with adriamycin the cumulative mortality was 40%. LV end-diastolic diameter(LVEDD) and LV end-systolic diameter(LVESD) were significantly increased in ADR-DCM group(all P< 0.01). FS , indices of LV contractile function, was significantly reduced in ADR-DCM group (P< 0.01). The level of MDA was higher in the ADR-DCM than the control group (P< 0.01).The gene and protein levels of LV MMP-2, MMP-9 were increased in ADR rat (P< 0.01), but there was no change in TIMP-1 (P> 0.05). Conclusion: Increased LV myocardial expression of MMP-2 and MMP-9 occurrs in ADR-DCM, MMPs may play an important role in the development of ADR-DCM.