Shimohama Takao, Suzuki Yoshiro, Noda Chiharu, Niwano Hiroe, Sato Kiyotaka, Masuda Takashi, Kawahara Katsumasa, Izumi Tohru
Department of Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Jpn Heart J. 2002 May;43(3):273-82. doi: 10.1536/jhj.43.273.
Although cardiac NHE1 is activated during myocardial ischemia and reperfusion injury, little is known about changes in expression in non-infarcted myocardium after acute myocardial infarction (AMI). The purpose of this study was to examine left ventricular function and region dependent NHE1 expression after myocardial infarction. Therefore, we produced two AMI models in rats, a small infarction model which was continuously ligated at the branches of the left coronary artery, and an extensive infarction model continuously ligated at the root of the artery. We examined NHE1 mRNA expression using RNase protection assay and protein levels using Western blot analysis in non-infarcted myocardium during the 24 hour period after AMI. The level of NHE1 mRNA and protein expression in the whole heart including the infarcted myocardium did not change after a small infarction. On the other hand, in the case of an extensive infarction, the levels of NHE1 mRNA and protein expression decreased significantly by 21.5% (P<0.05) and by 22.0% (P<0.05), respectively, in non-infarcted myocardium. Left ventricular systolic pressure (LVSP) decreased significantly by 13% and 38% with the branch and root ligation, respectively. However, left ventricular end-diastolic pressure (LVEDP) only increased with the root ligation. These results indicate that NHE1 expression decreased in response to extensive myocardial infarction only in non-infarcted myocardium. The present study may be important in furthering the understanding of NHE1 in myocardial infarction and suggests that decreased expression of NHE1 in non-infarcted myocardium may decrease the extent of cardiac cell injury.
尽管心肌缺血和再灌注损伤期间心脏NHE1会被激活,但对于急性心肌梗死(AMI)后非梗死心肌中NHE1表达的变化却知之甚少。本研究的目的是检测心肌梗死后左心室功能以及区域依赖性NHE1表达。因此,我们在大鼠中建立了两种AMI模型,一种是在左冠状动脉分支处持续结扎的小梗死模型,另一种是在动脉根部持续结扎的广泛梗死模型。我们在AMI后24小时内,使用核糖核酸酶保护试验检测非梗死心肌中NHE1 mRNA的表达,并使用蛋白质印迹分析检测蛋白质水平。小梗死模型后,包括梗死心肌在内的整个心脏中NHE1 mRNA和蛋白质表达水平均未发生变化。另一方面,在广泛梗死模型中,非梗死心肌中NHE1 mRNA和蛋白质表达水平分别显著下降了21.5%(P<0.05)和22.0%(P<0.05)。左心室收缩压(LVSP)在分支结扎和根部结扎时分别显著下降了13%和38%。然而,左心室舒张末期压力(LVEDP)仅在根部结扎时升高。这些结果表明,仅在广泛心肌梗死时,非梗死心肌中的NHE1表达才会下降。本研究对于进一步了解NHE1在心肌梗死中的作用可能具有重要意义,并提示非梗死心肌中NHE1表达的降低可能会减轻心肌细胞损伤的程度。