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二氢硫辛酸对缺氧及复氧过程中工作大鼠心脏的心脏保护作用。31P核磁共振研究。

Cardioprotective efficiency of dihydrolipoic acid in working rat hearts during hypoxia and reoxygenation. 31P nuclear magnetic resonance investigations.

作者信息

Assadnazari H, Zimmer G, Freisleben H J, Werk W, Leibfritz D

机构信息

Gustav-Embden-Zentrum der Biologischen Chemie, Universität, Frankfurt, Fed. Rep. of Germany.

出版信息

Arzneimittelforschung. 1993 Apr;43(4):425-32.

PMID:8494572
Abstract

The working rat heart model was used for 31P nuclear magnetic resonance (NMR) studies during normoxia, hypoxia and reoxygenation. Aortic flows of about 35 ml/min could be achieved which equals 65% of the values obtained outside the NMR magnet. Addition of dihydrolipoic acid (DHL) at a concentration of 0.3 mumol/l during hypoxia accelerated the recovery of aortic flow and stabilized it during reoxygenation. During hypoxia, inorganic phosphate contents (Pi) were significantly higher in controls. The phosphate shift indicated a pH decrease in control to 6.98, in DHL treated hearts the calculated pH was 7.15. During both hypoxia and reoxygenation, the phosphocreatinine (PCr) contents were higher in the DHL treated hearts than in controls. In the controls, saturation transfer measurements revealed a decrease of the flux PCr-->ATP during initial reoxygenation, whereas after addition of 0.3 mumol/l of DHL during hypoxia creatine kinase flux remained constant or increased. In isolated rat heart mitochondria, creatine kinase activities were measured under saturating and non-saturating concentrations of PCr. An increase in activity was observed under low PCr (non-saturating) conditions in the presence of 0.7 nmol DHL per mg of protein. At higher concentrations of DHL, creatine kinase activity was increased under all conditions. An increase in ATP synthesis in the working rat heart under influence of DHL is corroborated by NMR spectroscopy.

摘要

工作大鼠心脏模型用于常氧、缺氧和复氧期间的31P核磁共振(NMR)研究。可实现约35 ml/min的主动脉血流量,这相当于在NMR磁体外部获得的值的65%。在缺氧期间添加浓度为0.3 μmol/l的二氢硫辛酸(DHL)可加速主动脉血流量的恢复,并在复氧期间使其稳定。在缺氧期间,对照组的无机磷酸盐含量(Pi)显著更高。磷酸盐移位表明对照组的pH值降至6.98,在DHL处理的心脏中,计算出的pH值为7.15。在缺氧和复氧期间,DHL处理的心脏中的磷酸肌酸(PCr)含量均高于对照组。在对照组中,饱和转移测量显示在初始复氧期间PCr→ATP的通量降低,而在缺氧期间添加0.3 μmol/l的DHL后,肌酸激酶通量保持恒定或增加。在分离的大鼠心脏线粒体中,在PCr的饱和和非饱和浓度下测量肌酸激酶活性。在每毫克蛋白质存在0.7 nmol DHL的低PCr(非饱和)条件下,观察到活性增加。在所有条件下,在较高浓度的DHL下,肌酸激酶活性均增加。NMR光谱证实了DHL对工作大鼠心脏中ATP合成的增加作用。

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