A Natural p300-Specific Histone Acetyltransferase Inhibitor, Curcumin, in Addition to Angiotensin-Converting Enzyme Inhibitor, Exerts Beneficial Effects on Left Ventricular Systolic Function After Myocardial Infarction in Rats
A Natural p300-Specific Histone Acetyltransferase Inhibitor, Curcumin, in Addition to Angiotensin-Converting Enzyme Inhibitor, Exerts Beneficial Effects on Left Ventricular Systolic Function After Myocardial Infarction in Rats
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DOI：
10.1253/circj.cj-10-1072
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发表时间：
2011-09-01
影响因子：
3.3
通讯作者：
Hasegawa, Koji
中科院分区：
文献类型：
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作者：
Sunagawa, Yoichi;Morimoto, Tatsuya;Hasegawa, Koji
背景：姜黄素是一种天然的p300特异性组蛋白乙酰转移酶（HAT）抑制剂，可能具有治疗心力衰竭的潜力。然而，目前还不清楚姜黄素是否表现出有益的附加或协同作用，对传统的治疗与血管紧张素转换酶抑制剂（ACEIs.Methods和结果：大鼠进行假手术或左冠状动脉结扎。一周后，34只中度心肌梗死（MI）大鼠随机分为4组：溶剂对照组（n=8）、依那普利（ACEI，10 mg.kg（-1）.day（-1））单独组（n=8）、姜黄素（50 mg. kg（-1）day（-1））单独组（n=9）和依那普利+姜黄素组（n=9）。每天重复口服治疗，持续6周。4组治疗前超声心动图指标相似。治疗后，依那普利组（29.0 +/- 1.9%）和姜黄素组（30.8 +/- 1.7%）的左心室（LV）缩短分数（FS）显著高于溶剂组（19.7 +/- 1.6%）。值得注意的是，依那普利/姜黄素联合组的LVFS进一步增加（34.4 +/- 1.8%）。在组织学上，依那普利/姜黄素组合组的非梗死区的心肌细胞直径小于依那普利组。血管周围纤维化显着减少依那普利/姜黄素组相比，姜黄素group.Conclusions：天然无毒的饮食化合物，姜黄素，结合ACEI发挥有益的影响后MI左心室收缩功能的大鼠。(Circ J 2011; 75：2151-2159）
Background: A natural p300-specific histone acetyltransferase (HAT) inhibitor, curcumin, may have therapeutic potential for heart failure. However, it is unclear whether curcumin exhibits beneficial additive or synergistic effects on conventional therapy with angiotensin-converting enzyme inhibitors (ACEIs).Methods and Results: Rats were subjected to a sham operation or left coronary artery ligation. One week later, 34 rats with a moderate sized myocardial infarction (MI) were randomly assigned to 4 groups: solvents as control (n=8), enalapril (an ACEI, 10 mg.kg(-1).day(-1)) alone (n=8), curcumin (50 mg.kg(-1)day(-1)) alone (n=9) and enalapril plus curcumin (n=9). Daily oral treatment was repeated and continued for 6 weeks. Echocardiographic data were similar among the 4 groups before treatment. After treatment, left ventricular (LV) fractional shortening (FS) was significantly higher in the enalapril (29.0 +/- 1.9%) and curcumin (30.8 +/- 1.7%) groups than in the vehicle group (19.7 +/- 1.6%). Notably, LVFS further increased in the enalapril/curcumin combination group (34.4 +/- 1.8%). Histologically, cardiomyocyte diameter in the non-infarct area was smaller in the enalapril/curcumin combination group than in the enalapril group. Perivascular fibrosis was significantly reduced in the enalapril/curcumin group compared with the curcumin group.Conclusions: A natural non-toxic dietary compound, curcumin, combined with an ACEI exerts beneficial effects on post-MI LV systolic function in rats. (Circ J 2011; 75: 2151-2159)