二氢黄酮醇通过防止山羊非梗死区心肌细胞凋亡来减少梗死后左心室重构。

Dihydroxyflavonol reduces post-infarction left ventricular remodeling by preventing myocyte apoptosis in the non-infarcted zone in goats.

作者信息

Wang Sheng, Fei Ke, Xu Ya-wei, Wang Liang-xu, Chen Yan-qin

机构信息

Department of Cardiothoracic Surgery, Shanghai 10th People's Hospital, Tongji University, Shanghai, China.

出版信息

Chin Med J (Engl). 2009 Jan 5;122(1):61-7.

PMID:19187619

Abstract

BACKGROUND

Myocyte apoptosis is considered to be the major causative factor of left ventricular (LV) remodeling following myocardial infarction (MI). We previously reported that 3', 4'-dihydroxyflavonol (DiOHF), was able to suppress oxidative stress and preserve the expression of endothelial nitric oxide synthase during myocardial reperfusion injury, which may benefit the reduction of myocyte apoptosis. We therefore aimed to evaluate the potential actions of DiOHF against myocyte apoptosis and post-infarction LV remodeling in this study.

METHODS

Following experimental MI, surgical instrumented goats were randomly assigned into vehicle and DiOHF (2 mg/kg; i.v., daily) groups to receive 4 weeks of reperfusion with corresponding treatments. LV pressure recordings and echocardiogram were performed at baseline, 2 and 4 weeks of reperfusion. Myocardial tissues were collected in the end to determine infarct size and apoptosis related assays.

RESULTS

LV end-diastolic volume and diameter were significantly increased 4 weeks after MI in the vehicle group, accompanied by reduced posterior wall thickness, septal thickness and LV mass, whereas those changes were markedly prevented by DiOHF treatment. Similarly, significantly reduced infarct size was found in DiOHF group as compared to vehicle group, and DiOHF dramatically inhibited the increase in LV end-diastolic pressure and the reductions in ejection fraction, fraction shortening and dP/dt(max). Moreover, DiOHF treatment significantly reduced the extent of myocyte apoptosis detected by TUNEL assay, enhanced the protein expression of caspase-3, Fas, Bax and cytochrome c in the non-infarcted myocardium in comparison to vehicle.

CONCLUSIONS

Daily DiOHF treatment during the reperfusion period after MI in the ovine hearts markedly reduced the magnitude of post-infarction LV remodeling through the inhibition of myocyte apoptosis in the remote non-infarcted myocardium.

摘要

背景

心肌细胞凋亡被认为是心肌梗死（MI）后左心室（LV）重构的主要致病因素。我们之前报道过，3'，4'-二羟基黄酮醇（DiOHF）能够抑制氧化应激，并在心肌再灌注损伤期间维持内皮型一氧化氮合酶的表达，这可能有助于减少心肌细胞凋亡。因此，我们旨在评估DiOHF在本研究中对心肌细胞凋亡和梗死后左心室重构的潜在作用。

方法

实验性心肌梗死后，将手术植入仪器的山羊随机分为溶剂对照组和DiOHF组（2mg/kg；静脉注射，每日一次），接受4周的再灌注及相应治疗。在基线、再灌注2周和4周时进行左心室压力记录和超声心动图检查。最后收集心肌组织以确定梗死面积和凋亡相关检测。

结果

溶剂对照组在心肌梗死后4周时左心室舒张末期容积和直径显著增加，同时后壁厚度、室间隔厚度和左心室质量降低，而DiOHF治疗显著预防了这些变化。同样，与溶剂对照组相比，DiOHF组梗死面积显著减小，并且DiOHF显著抑制了左心室舒张末期压力的升高以及射血分数、缩短分数和dP/dt（max）的降低。此外，与溶剂对照组相比，DiOHF治疗显著降低了TUNEL检测法检测到的心肌细胞凋亡程度，增强了非梗死心肌中caspase-3、Fas、Bax和细胞色素c的蛋白表达。