Imahashi K, Hashimoto K, Yamaguchi H, Nishimura T, Kusuoka H
Division of Tracer Kinetics, Biomedical Research Center, Osaka University Medical School, Suita, Osaka, 565, Japan.
J Mol Cell Cardiol. 1998 Mar;30(3):509-17. doi: 10.1006/jmcc.1997.0615.
To elucidate the contribution of reduced activity of Na+/H+ exchange in streptozotocin-induced diabetic hearts against stunning, intracellular Na+ concentration ([Na+]i) was measured in isolated rat hearts using 23Na-MRS. The recovery of left ventricular developed pressure in hearts reperfused after 15 min global ischaemia at 37 degreesC was significantly better in diabetic ones (102.9+/-2.0% of pre-ischemic level, mean+/-s.e., n=6; P<0.05), and non-diabetic ones pre-treated with potent Na+/H+ exchange inhibitor, EIPA (1 mu mol/l; 93.8+/-2.3%, n=5; *P<0.05) than non-treated, non-diabetic hearts (75.1+/-2.5%, n=8). When diabetic hearts were pre-treated with EIPA, the recovery (101.2+/-2.6%, n=5) was identical to that of non-treated, diabetic hearts. [Na+]i in non-diabetic hearts increased to 329.1+/-8.1% of pre-ischemic level during 15 min ischemia, whereas the increase in [Na+]i in diabetic hearts significantly suppressed to 199.8+/-10.3% (P<0.001). EIPA attenuated the increase of [Na+]i during ischemia to 189.1+/-9.0% in non-diabetic hearts ( P<0.001) and to 155.3+/-4.6% in diabetic hearts (P<0.05). Thus, the EIPA-dependent Na+ accumulation during ischemia, i.e. Na+ influx probably mostly via Na+/H+ exchange was smaller in diabetic hearts by 69.7% compared with that in non-diabetic hearts. These results indicate that the cardiac protection against stunning in streptozotocin-induced diabetic hearts is mediated by the attenuation of Na+ accumulation during ischemia, which is caused by the reduced activity in Na+/H+ exchanger.
为阐明链脲佐菌素诱导的糖尿病心脏中钠氢交换活性降低对心肌顿抑的作用，采用23Na磁共振波谱法测量离体大鼠心脏的细胞内钠浓度（[Na+]i）。在37℃下进行15分钟全心缺血后再灌注的心脏中，糖尿病心脏（102.9±2.0%的缺血前水平，平均值±标准误，n = 6；P<0.05）以及用强效钠氢交换抑制剂EIPA（1μmol/L）预处理的非糖尿病心脏（93.8±2.3%，n = 5；*P<0.05）的左心室舒张末压恢复情况明显优于未处理的非糖尿病心脏（75.1±2.5%，n = 8）。当糖尿病心脏用EIPA预处理时，其恢复情况（101.2±2.6%，n = 5）与未处理的糖尿病心脏相同。非糖尿病心脏在15分钟缺血期间[Na+]i增加到缺血前水平的329.1±8.1%，而糖尿病心脏中[Na+]i的增加显著抑制至199.8±10.3%（P<0.001）。EIPA使非糖尿病心脏缺血期间[Na+]i的增加减弱至189.1±9.0%（P<0.001），使糖尿病心脏中[Na+]i的增加减弱至155.3±4.6%（P<0.05）。因此，与非糖尿病心脏相比，糖尿病心脏缺血期间依赖EIPA的钠蓄积，即可能主要通过钠氢交换的钠内流减少了69.7%。这些结果表明，链脲佐菌素诱导的糖尿病心脏对心肌顿抑的心脏保护作用是通过缺血期间钠蓄积的减弱介导的，这是由钠氢交换体活性降低引起的。
