摘要
观察结扎左冠状动脉前降支复制的心肌梗死大鼠模型术后 2、4和 8周的血流动力学、心室重塑指标及梗死周围 4mm的心肌组织肌型肉碱棕榈酰转移酶、中链酰基辅酶A脱氢酶和过氧化物酶体增殖剂活化受体α基因表达的变化 ,以探讨无或伴有心力衰竭的大鼠心肌梗死后左心室重塑与局部脂肪酸氧化酶基因表达的关系。术后 2周右室即出现肥厚 ,与假手术组比较 ,梗死周围的心肌组织肌型肉碱棕榈酰转移酶、中链酰基辅酶A脱氢酶和过氧化物酶体增殖剂活化受体αmRNA表达下调 (分别为 2 7%、35 %和 2 0 % ,P <0 .0 5 ) ;8周时大鼠出现明显心力衰竭 ,左心室略有肥厚 ,上述基因表达比 2周时显著下调 (分别为 5 2 %、6 0 %和 4 4 % ,P <0 .0 5 )。以上表明心肌梗死后大鼠从代偿性重塑到心力衰竭的发展过程中均存在脂肪酸氧化酶基因表达下调 ;过氧化物酶体增殖剂活化受体α在心肌梗死后心肌脂肪酸氧化酶基因的表达中可能起重要的调控作用。
Aim To determine whether left ventricular remodeling with or without onset heart failure after myocardial infarction is associated with the regional changes in the gene expression of fatty acid metabolism. Methods Myocardial infarction(MI) was induced in rats by ligation of the left anterior descending coronary artery. Hemodyanmics, ventricular remodeling parameters were investigated in the experimental and sham operated animals(SH) at 2, 4, 8 week after operation. In infarcted hearts, the peri infarction region(4 mm zone surrounding the region) were separated for gene expression analysis of the rate limiting enzyme[muscle carnitine palmitoyltransferase I (M CPT I)], key enzyme[medium chain Acyl CoA dehydrogenase(MCAD)] of fatty acid oxidation and nuclear transcription factor [peroxisome proliferator activated receptors α(PPAR α)]. Results At 2 weeks after LAD ligation, when right ventricular hypertrophy was present without signs of heart failure, mRNA expression of M CPT I, MCAD and PPAR α was reduced in the peri infarction regions[27%,35%and 20% respectively in MI 2w vs SH; ([WTBX]P<0.05)]. Until 8 weeks, left ventricle displayed a little hypertrophy with heart failure, there was significant downregulation in mRNA expression of M CPT I, MCAD and PPAR α in the peri infarction regions . Until 8 weeks, left ventricle displayed a little hypertrophy with heart failure, there was significant downregulation in mRNA expression of M CPT I, MCAD and PPAR α in the peri infarction regions [reduced 52%,60% and 44% respectively in MI 8w /SH 8w vs MI 2w /SH 2w ;([WTBX]P<0.05)]. . Conclusion In rats with MI, progression from compensated remodeling to heart failure is associated with gene expression downregulation of fatty acid oxidation in the peri infarction region. Downregulation of PPAR α mRNA displays that PPAR α may be a very important factor that regulates cardiac fatty acid oxidation in rats subsequent to myocardial infarction.
出处
《中国动脉硬化杂志》
CAS
CSCD
2003年第2期143-146,共4页
Chinese Journal of Arteriosclerosis
