Marina Prendes M G, García J V, Testoni G, Fernández M A, Perazzo J C, Savino E A, Varela A
Cátedra de Fisiología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires and IQUIMEFA-CONICET, Buenos Aires, Argentina.
Arch Physiol Biochem. 2006 Feb;112(1):31-6. doi: 10.1080/13813450500500357.
To assess whether glycolysis, Na+-H+ exchange and oxidation of fatty acid derived from endogenous lipolysis are involved in the beneficial effects of 24-h fasting on the ischaemic - reperfused heart, it was studied the effects of inhibiting Na+ - H+ exchange using 10 muM dimethylamiloride and fatty acid oxidation using 2 mM oxfenicine, on the functional activity, lactate production and cell viability measured with tetrazolium stain. Since fasting accelerates heart fatty acid oxidation, data were compared to those from fed rats; using Langendorff perfused (glucose 10 mM) hearts of 250-350 g Wistar rats exposed to 25 min ischaemia - 30 min reperfusion. Fasting reduced the ischaemic rise of end diastolic pressure (contracture), improved recovery of contraction and lowered lactate production in comparison with the fed whereas cellular viability was similar in both groups. Dimethylamiloride improved the recovery of contraction (fed control 24 +/- 9%, fed treated 68 +/- 11%, P < 0.05 at the end of reperfusion), attenuated the contracture (fed control 40 +/- 9%, fed treated 24 +/- 11%, P < 0.05 at the beginning of reperfusion) and reduced lactate production in the fed group and increased cellular viability in both groups (fed control 21 +/- 6%, fed treated 69 +/- 7%, P < 0.05, and fasted control 18 +/- 7%, fasted treated 53 +/- 8%, P < 0.05). Oxfenicine reduced the recovery of contraction (fasted control 88 +/- 6%, fasted treated 60 +/- 11%, P < 0.05) and increased lactate production of fasted group and attenuated the contracture in the fed. These data suggest that beneficial effects of fasting owe, at least in part, to a lowered glycolysis probably secondary to the increased fatty acid oxidation and to the accumulation of energy supplying acyl esters. Dimethylamiloride slowing of glycolysis might explain functional improvement, whereas it seems unrelated to the protection on cell viability.
为了评估糖酵解、钠氢交换以及内源性脂肪分解产生的脂肪酸氧化是否参与24小时禁食对缺血再灌注心脏的有益作用，研究了使用10 μM二甲基amiloride抑制钠氢交换以及使用2 mM氧苯尼卡因抑制脂肪酸氧化，对用四氮唑染色测量的功能活性、乳酸生成和细胞活力的影响。由于禁食会加速心脏脂肪酸氧化，因此将数据与喂食大鼠的数据进行比较；使用体重250 - 350 g的Wistar大鼠的Langendorff灌注（葡萄糖10 mM）心脏，使其经历25分钟缺血 - 30分钟再灌注。与喂食组相比，禁食降低了舒张末期压力（挛缩）的缺血性升高，改善了收缩恢复并降低了乳酸生成，而两组的细胞活力相似。二甲基amiloride改善了收缩恢复（喂食对照组24±9%，喂食处理组68±11%，再灌注结束时P<0.05），减轻了挛缩（喂食对照组40±9%，喂食处理组24±11%，再灌注开始时P<0.05），并降低了喂食组的乳酸生成，且增加了两组的细胞活力（喂食对照组21±6%，喂食处理组69±7%，P<0.05；禁食对照组18±7%，禁食处理组53±8%，P<0.05）。氧苯尼卡因降低了收缩恢复（禁食对照组88±6%，禁食处理组60±11%，P<0.05），增加了禁食组的乳酸生成，并减轻了喂食组的挛缩。这些数据表明，禁食的有益作用至少部分归因于糖酵解降低，这可能继发于脂肪酸氧化增加和能量供应酰基酯的积累。二甲基amiloride减缓糖酵解可能解释了功能改善，而这似乎与对细胞活力的保护无关。
