Pisarenko O I, Studneva I M, Shulzhenko V S, Korchazhkina O V, Kapelko V I
Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia.
Biochem Mol Med. 1995 Aug;55(2):138-48. doi: 10.1006/bmme.1995.1044.
The effects of aspartate (Asp) and 2-oxoglutarate (2-OG) on metabolism and function of isolated rat heart during hypoxia and reoxygenation were studied. Hearts were subjected to oxygenated perfusion with Krebs-Henseleit buffer supplied with 11 mM glucose (20 min) and anoxic perfusion with the buffer saturated with N2 (20 min), followed by reoxygenation (30 min). The substrate concentrations in the perfusate were 3.5 mM each. The additives had no effect on the energy metabolism and function of the oxygenated heart despite a two-fold rise in myocardial Asp and 2-OG. Substrate supplementation during anoxic perfusion resulted in reduced lactate dehydrogenase release and less depression of cardiac function. Prevention of Asp, glutamate, and 2-OG degradation in hypoxic myocardium was accompanied by relief of glycolytic flux and better preservation of ATP, phosphocreatine (PCr), and total creatine (Cr). Reoxygenation without the additives after supplemented anoxic perfusion failed to improve recovery of high-energy phosphates and cardiac function compared to control. However, during reoxygenation with the additives the treated hearts showed less cell membrane damage and enhanced recovery of contractile and pump function. These effects were associated with higher myocardial contents of ATP, PCr, and adenine nucleotides and a smaller Cr loss during reoxygenation. A more effective restoration of oxidative metabolism was related to promoted glucose oxidation due to replenishment of the malate-aspartate shuttle reactants. The results substantiate the use of substrates of cytosolic aspartate aminotransferase for myocardial protection against hypoxia/reoxygenation stress.
研究了天冬氨酸（Asp）和2-氧代戊二酸（2-OG）对缺氧和复氧期间离体大鼠心脏代谢和功能的影响。心脏先用含11 mM葡萄糖的Krebs-Henseleit缓冲液进行有氧灌注（20分钟），然后用饱和氮气的缓冲液进行无氧灌注（20分钟），随后复氧（30分钟）。灌注液中的底物浓度均为3.5 mM。尽管心肌Asp和2-OG增加了两倍，但添加剂对有氧心脏的能量代谢和功能没有影响。无氧灌注期间补充底物可减少乳酸脱氢酶释放，并减轻心脏功能的抑制。防止缺氧心肌中Asp、谷氨酸和2-OG的降解伴随着糖酵解通量的缓解以及ATP、磷酸肌酸（PCr）和总肌酸（Cr）的更好保存。与对照组相比，补充无氧灌注后不添加添加剂的复氧未能改善高能磷酸盐和心脏功能的恢复。然而，在添加添加剂的复氧过程中，处理过的心脏显示出较少的细胞膜损伤，并增强了收缩和泵功能的恢复。这些作用与复氧期间心肌中较高的ATP、PCr和腺嘌呤核苷酸含量以及较小的Cr损失有关。氧化代谢的更有效恢复与由于苹果酸-天冬氨酸穿梭反应物的补充而促进的葡萄糖氧化有关。结果证实了使用胞质天冬氨酸转氨酶的底物来保护心肌免受缺氧/复氧应激。
