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机械性超负荷大鼠心脏中左旋肉碱转运减少。

Decreased L-carnitine transport in mechanically overloaded rat hearts.

作者信息

el Alaoui-Talibi Z, Moravec J

机构信息

I.N.S.E.R.M. U2, Hôpital Léon Bernard, Limeil-Grévannes, France.

出版信息

Basic Res Cardiol. 1987;82 Suppl 2:223-31. doi: 10.1007/978-3-662-11289-2_22.

DOI:10.1007/978-3-662-11289-2_22
PMID:3663018
Abstract

The transport of L[14C] carnitine was studied in rat hearts with a three-month-old aorto-caval fistula. Tissue TG content was determined in order to assess the state of FFA utilization. The hearts were perfused with a bicarbonate buffer containing 11 mM glucose and variable concentrations (10-200 microM) of L[14C] carnitine. In some experiments, the active component of carnitine transport was suppressed by the adjunction of 0.05 mM mersalyl acid. The subtraction of passive from total transport allowed us to reconstruct the saturation curves of the net active transport of L-carnitine. Our results suggest that at physiological carnitine concentration (50 microM) the uptake of L-carnitine is significantly depressed in mechanically overloaded hearts. These changes are not related to alterations of coronary perfusion, since coronary flow rates (ml/min/g dry wt) are quite comparable in both groups tested. According to the Lineweaver-Burk analysis of the kinetics of saturable transport, the affinity of the membrane carrier for L-carnitine is considerably diminished in the overloaded hearts (Km[carnitine] 125 instead of 83 microM). The alterations of the kinetics of carnitine transport do not seems to be related to the decrease of the transmembrane gradient of sodium: the intracellular sodium content of the hypertrophied, but non-failing, hearts is quite similar to that of control hearts. In addition, carnitine deficiency does not lead to TG accumulation, at least under in situ conditions.

摘要

在患有三个月大主动脉 - 腔静脉瘘的大鼠心脏中研究了L-[¹⁴C]肉碱的转运。测定组织甘油三酯(TG)含量以评估游离脂肪酸(FFA)的利用状态。用含有11 mM葡萄糖和可变浓度(10 - 200 μM)L-[¹⁴C]肉碱的碳酸氢盐缓冲液灌注心脏。在一些实验中,通过添加0.05 mM的汞撒利酸抑制肉碱转运的活性成分。从总转运中减去被动转运,使我们能够重建L-肉碱净主动转运的饱和曲线。我们的结果表明,在生理肉碱浓度(50 μM)下,机械性过载心脏中L-肉碱的摄取显著降低。这些变化与冠状动脉灌注的改变无关,因为在测试的两组中冠状动脉流速(ml/min/g干重)相当。根据对可饱和转运动力学的Lineweaver-Burk分析,过载心脏中膜载体对L-肉碱的亲和力显著降低(肉碱的Km值为125 μM,而不是83 μM)。肉碱转运动力学的改变似乎与钠的跨膜梯度降低无关:肥厚但未衰竭的心脏的细胞内钠含量与对照心脏相当。此外,至少在原位条件下,肉碱缺乏不会导致TG积累。

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