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高脂肪酸水平对糖尿病大鼠缺血性心脏功能恢复的影响。

Effects of high levels of fatty acids on functional recovery of ischemic hearts from diabetic rats.

作者信息

Lopaschuk G D, Saddik M, Barr R, Huang L, Barker C C, Muzyka R A

机构信息

Department of Pediatrics, University of Alberta, Edmonton, Canada.

出版信息

Am J Physiol. 1992 Dec;263(6):E1046-53. doi: 10.1152/ajpendo.2006.263.6.E1046.

Abstract

In this study we determined the effects of high levels of fatty acids on recovery of heart function when present either during or after ischemia. Isolated working hearts from 6-wk streptozotocin diabetic and control rats perfused with 11 mM glucose were subjected to 25 min of global ischemia followed by 30 min of aerobic reperfusion. Four groups were studied: 1) 1.2 mM palmitate present before, during, and after ischemia; 2) 1.2 mM palmitate present before and during ischemia, followed by reperfusion in the absence of palmitate; 3) no palmitate before and during ischemia, followed by 1.2 mM palmitate during reperfusion; and 4) no palmitate before and during ischemia or during reperfusion. In control hearts, palmitate during reperfusion depressed recovery of function regardless of whether palmitate was present or absent during ischemia. In contrast, palmitate present during reperfusion did not depress recovery of mechanical function in the diabetic rat hearts. However, the presence of palmitate during ischemia itself in diabetic rat hearts was detrimental to recovery of mechanical function. The presence of palmitate during ischemia resulted in an accelerated rate of ATP loss and a decreased rate of lactate accumulation during ischemia, although this effect was similar in control and diabetic rat hearts. Our results demonstrate that high concentrations of fatty acids depress functional recovery of control rat hearts during the reperfusion period but depress recovery of function in diabetic rat hearts when present during ischemia itself.

摘要

在本研究中,我们测定了高水平脂肪酸在缺血期间或之后存在时对心脏功能恢复的影响。用11 mM葡萄糖灌注来自6周龄链脲佐菌素糖尿病大鼠和对照大鼠的离体工作心脏,使其经历25分钟的全心缺血,随后进行30分钟的有氧再灌注。研究了四组:1)缺血前、缺血期间和缺血后存在1.2 mM棕榈酸酯;2)缺血前和缺血期间存在1.2 mM棕榈酸酯,随后在无棕榈酸酯的情况下进行再灌注;3)缺血前和缺血期间无棕榈酸酯,随后在再灌注期间存在1.2 mM棕榈酸酯;4)缺血前、缺血期间或再灌注期间无棕榈酸酯。在对照心脏中,无论缺血期间是否存在棕榈酸酯,再灌注期间的棕榈酸酯都会抑制功能恢复。相比之下,再灌注期间存在的棕榈酸酯不会抑制糖尿病大鼠心脏的机械功能恢复。然而,糖尿病大鼠心脏缺血期间本身存在棕榈酸酯对机械功能恢复是有害的。缺血期间存在棕榈酸酯导致缺血期间ATP损失速率加快和乳酸积累速率降低,尽管这种效应在对照大鼠和糖尿病大鼠心脏中相似。我们的结果表明,高浓度脂肪酸在再灌注期会抑制对照大鼠心脏的功能恢复,但在糖尿病大鼠心脏缺血期间本身存在时会抑制功能恢复。

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