尼可地尔对异丙肾上腺素致心肌肥厚大鼠心肌MMP-9及TIMP-1表达的影响

Effect of nicorandil on MMP-9 and TIMP-1 expression in myocardium of a rat model of myocardial hypertrophy induced by isoprenaline

目的探讨尼可地尔对异丙肾上腺素(ISO)所致心肌肥厚大鼠心肌基质金属蛋白酶9(MMP-9)和金属蛋白酶组织抑制因子1(TIMP-1)表达的影响。方法采用皮下注射ISO制备心肌肥厚模型。30只SD大鼠随机均分为对照组、模型组和尼可地尔组。测定心脏质量指数(HMI)和左心室质量指数(LVMI),酶联免疫吸附法测血浆中脑钠肽(BNP)含量,免疫组化法测定心肌组织MMP-9和TIMP-1表达。结果与对照组相比,模型组HMI、LVMI、BNP水平、MMP-9表达均明显增加(P<0.05),TIMP-1表达降低(P<0.05)。与模型组相比,尼可地尔组HMI、LVMI、BNP水平、MMP-9表达均明显降低(P<0.05),TIMP-1表达增加(P<0.05)。结论 ISO诱导心肌肥厚,MMPs/TIMPs系统平衡被破坏。尼可地尔可通过调节心肌组织MMP-9/TIMP-1的表达来逆转细胞外基质(ECM)重塑,从而预防心肌肥厚的发生。

Objective To investigate the effect of nicorandil on matrix metalloproteinases-9 （MMP-9） and tissue in- hibitors of metalloproteinases-1 （ TIMP-1 ） expression in myocardium of a rat model of myocardial hypertrophy in- duced by isoprenaline（ISO）. Methods Myocardial hypertrophy model was established using subcutaneous injec- tion of ISO. 30 SD rats were randomized into control group, model group and nicorandil group. Heart mass index （HMI） and left ventricular mass index （LVMI） were calculated. The serum level of brain natriuretic peptide （BNP） was measured by enzyme-linked immunosorbent assay. Myocardium MMP-9 and TIMP-1 expression was an- alyzed by immunohistochemistry. Results Comparing with the control group, HMI, LVMI, BNP and the expres- sion of MMP-9 in model group significantly increased （P 〈 0.05 ） , and the expression of TIMP-1 significantly de- creased（P 〈 0. 05）. In nicorandil group, comparing with the model group, HMI, LVMI, BNP and the expression of MMP-9 significantly decreased （ P 〈 0. 05 ） , and the expression of TIMP-1 was significantly increased （ P 〈 0. 05 ）. Conclusion There is a destructive unbalance in the MMPs/TIMPs system in rat myocardial hypertrophy in- duced by ISO. Nicorandil could reverse extracellular matrix （ECM） remodeling and prevent cardiac hypertrophy, which is associated with the regulation of myocardium MMP-9 and TIMP-1 expression.