The role of Na+/H+ exchanger in Ca2+ overload and ischemic myocardial damage in hearts from type 2 diabetic db/db mice.
The role of Na+/H+ exchanger in Ca2+ overload and ischemic myocardial damage in hearts from type 2 diabetic db/db mice.
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DOI：
10.1186/1475-2840-11-33
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发表时间：
2012-04-11
影响因子：
9.3
通讯作者：
Yoshimura M
中科院分区：
文献类型：
--
作者：
Anzawa R;Seki S;Nagoshi T;Taniguchi I;Feuvray D;Yoshimura M
据报道，在2型糖尿病小鼠心脏中，缺血期间细胞内Na+通过Na+/H+交换剂（NHE）增加较多。我们研究了NHE在诱导2型糖尿病小鼠心脏缺血再灌注过程中胞浆Ca 2+浓度（[Ca 2 +]i）变化和心室功能改变中的作用。对雄性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4μM 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。[Ca2+]i通过监测500 nm处的fura-2荧光（激发波长为340和380 nm）来测量，同时测量左心室（LV）压力。在缺血后再灌注期间，db/db心脏表现出比db/+心脏更低的LV发展压力恢复。在缺血和再灌注期间，糖尿病心脏的舒张[Ca 2 +]i增加到比对照心脏更高的水平。在NHE抑制剂cariporide的存在下，糖尿病心脏缺血再灌注期间细胞质Ca 2+超载的这种增加显著减少。这伴随着再灌注时心室功能恢复的显著改善，如舒张压增加较低和发展压力恢复增加所示。NHE在增强缺血-再灌注期间细胞质Ca 2+超载和严重损害2型糖尿病db/db小鼠心脏缺血后心功能中起关键作用。
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 Ca2+ concentration ([Ca2+]i) 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 4μM of the Ca2+ indicator fura-2. The hearts were exposed to no-flow ischemia for 15 minutes and then reperfused. [Ca2+]i 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 [Ca2+]i was increased to a greater level in diabetic hearts than in the control hearts during ischemia and reperfusion. Such an increase in cytoplasmic Ca2+ 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 Ca2+ overload during ischemia-reperfusion and severely impairing post-ischemic cardiac function in hearts from type 2 diabetic db/db mice.
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DOI：
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发表时间：
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影响因子：
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