Iijima K, Geshi E, Nomizo A, Arata Y, Katagiri T
Third Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Jpn Circ J. 1998 Jun;62(6):449-54. doi: 10.1253/jcj.62.449.
The purpose of this study was to investigate the function of sarcoplasmic reticulum (SR) and the role of angiotensin II type 1 receptor (AT1) in ventricular remodeling in non-infarcted areas after myocardial infarction (MI). MI was produced in anesthetized Sprague-Dawley rats (10-12-weeks old) by ligation of the left anterior descending coronary artery. Four weeks after MI, hemodynamic measurements were performed. SR Ca2+-ATPase activity and mRNA (SERCA2a) and AT1 mRNA (AT1a, AT1b) were analyzed. Left ventricular end-diastolic pressure was higher and left ventricular dp/dt was significantly lower in the MI group. In non-infarcted areas in the MI group, myocardial transverse diameter was significantly greater and both Ca2+-ATPase activity in the SR and SERCA2a level decreased. The AT1a level was higher in non-infarcted areas than in controls, whereas the AT1b mRNA expression level was unchanged. These results suggest that, in the ventricular remodeling after MI, alterations in SR protein and its mRNA in non-infarcted myocardium help initiate heart failure and that Ca overload caused by the up-regulation of AT1a mRNA is an important cause of alteration in SR function.
本研究旨在探讨心肌梗死（MI）后非梗死区域肌浆网（SR）的功能以及血管紧张素II 1型受体（AT1）在心室重构中的作用。通过结扎左冠状动脉前降支，在麻醉的10 - 12周龄Sprague-Dawley大鼠中制造MI模型。MI后4周，进行血流动力学测量。分析SR Ca2 + -ATP酶活性、mRNA（SERCA2a）和AT1 mRNA（AT1a、AT1b）。MI组左心室舒张末期压力较高，左心室dp/dt显著较低。在MI组的非梗死区域，心肌横径显著增大，SR中的Ca2 + -ATP酶活性和SERCA2a水平均降低。非梗死区域的AT1a水平高于对照组，而AT1b mRNA表达水平未改变。这些结果表明，在MI后的心室重构中，非梗死心肌中SR蛋白及其mRNA的改变有助于引发心力衰竭，并且AT1a mRNA上调导致的钙超载是SR功能改变的重要原因。
