Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan.
Cardiovasc Diabetol. 2012 Apr 11;11:33. doi: 10.1186/1475-2840-11-33.
A higher increase in intracellular Na(+) via Na(+)/H(+) exchanger (NHE) during ischemia has been reported in type 2 diabetic mouse hearts. We investigated the role of NHE in inducing changes in cytoplasmic Ca(2+) concentration (Ca(2+)) and alterations in ventricular function during ischemia-reperfusion in type 2 diabetic mouse hearts.
Hearts from male type 2 diabetic db/db (12-15 weeks old) and age-matched control db/+ mice were subjected to Langendorff perfusion and loaded with 4 μM of the Ca(2+) indicator fura-2. The hearts were exposed to no-flow ischemia for 15 minutes and then reperfused. Ca(2+) was measured by monitoring fura-2 fluorescence at 500 nm (excitation wavelengths of 340 and 380 nm), while left ventricular (LV) pressure was simultaneously measured.
db/db hearts exhibited a lower recovery of LV developed pressure than db/+ hearts during reperfusion following ischemia. Diastolic Ca(2+) was increased to a greater level in diabetic hearts than in the control hearts during ischemia and reperfusion. Such an increase in cytoplasmic Ca(2+) overload during ischemia-reperfusion in diabetic hearts was markedly reduced in the presence of the NHE inhibitor cariporide. This was accompanied by a significantly improved recovery of ventricular function on reperfusion, as shown by a lower increase in diastolic pressure and increased recovery of developed pressure.
NHE plays a key role in enhancing cytoplasmic Ca(2+) overload during ischemia-reperfusion and severely impairing post-ischemic cardiac function in hearts from type 2 diabetic db/db mice.
据报道，在 2 型糖尿病小鼠心脏中，缺血期间通过钠/氢交换器（NHE）的细胞内 Na(+)增加幅度更高。我们研究了 NHE 在诱导缺血再灌注期间细胞质 Ca(2+)浓度 (Ca(2+))变化和心室功能改变中的作用。
雄性 2 型糖尿病 db/db（12-15 周龄）和年龄匹配的对照 db/+ 小鼠的心脏进行 Langendorff 灌注，并加载 4 μM 的 Ca(2+)指示剂 fura-2。心脏暴露于无血流缺血 15 分钟，然后再灌注。通过监测 fura-2 荧光在 500nm（激发波长为 340nm 和 380nm）来测量 Ca(2+)，同时测量左心室（LV）压力。
与 db/+ 心脏相比，db/db 心脏在缺血后再灌注期间的 LV 发展压恢复较低。与对照心脏相比，糖尿病心脏在缺血和再灌注期间舒张期 Ca(2+)增加到更高水平。在 NHE 抑制剂 cariporide 的存在下，糖尿病心脏在缺血再灌注期间这种细胞质 Ca(2+)超载的增加明显减少。这伴随着再灌注时心室功能的显著改善，表现为舒张压升高幅度较低和发展压的恢复增加。
NHE 在增强缺血再灌注期间细胞质 Ca(2+)超载以及严重损害 2 型糖尿病 db/db 小鼠心脏缺血后心脏功能方面发挥关键作用。
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