Prasad M R, Popescu L M, Moraru I I, Liu X K, Maity S, Engelman R M, Das D K
Department of Surgery, University of Connecticut School of Medicine, Farmington 06032.
Am J Physiol. 1991 Mar;260(3 Pt 2):H877-83. doi: 10.1152/ajpheart.1991.260.3.H877.
We investigated the role of phospholipase A2 (PLA2) and phospholipase C (PLC) in myocardial phosholipid degradation and cellular injury during reperfusion of ischemic myocardium. For this purpose, isolated rat hearts were perfused with isotopic arachidonic acid to label its membrane phospholipids. Hearts preperfused with antiphospholipase A2 (anti-PLA2) retained a significantly higher amount of radiolabel in phosphatidylcholine and phosphatidylinositol and a corresponding lower amount of radiolabel in lysophosphatidylcholine and nonesterified fatty acids (P less than 0.05) after 30 min of reperfusion following 30 min of normothermic global ischemia compared with hearts preperfused with nonimmune immunoglobulin G. In similar experiments, antiphospholipase C (anti-PLC)-treated hearts were associated with significantly (P less than 0.05) higher radiolabel in all phospholipids and lower radiolabel in diacyglycerol compared with nonimmune immunoglobulin G-treated hearts. Measurement of phospholipase activity in subcellular organelles of these hearts showed decreased PLA2 activity in cytosol, mitochondria, and microsomes of anti-PLA2-treated hearts and decreased PLC activity of microsomes in anti-PLC-treated hearts. Furthermore, both the antiphospholipases attenuated the release of creatine kinase and lactate dehydrogenase into perfusate and increased contractility as well as coronary flow in the reperfused hearts. Results of this study suggest that both PLA2 and PLC are involved in the degradation of phospholipids and cellular injury that occur during reperfusion of ischemic myocardium.
我们研究了磷脂酶A2（PLA2）和磷脂酶C（PLC）在缺血心肌再灌注期间心肌磷脂降解和细胞损伤中的作用。为此，用同位素花生四烯酸灌注离体大鼠心脏以标记其膜磷脂。与用非免疫免疫球蛋白G预灌注的心脏相比，用抗磷脂酶A2（抗PLA2）预灌注的心脏在常温全心缺血30分钟后再灌注30分钟时，磷脂酰胆碱和磷脂酰肌醇中保留的放射性标记量明显更高，而溶血磷脂酰胆碱和非酯化脂肪酸中的放射性标记量相应更低（P<0.05）。在类似实验中，与用非免疫免疫球蛋白G处理的心脏相比，用抗磷脂酶C（抗PLC）处理的心脏所有磷脂中的放射性标记明显更高（P<0.05），而二酰甘油中的放射性标记更低。对这些心脏亚细胞器中磷脂酶活性的测量显示，抗PLA2处理的心脏的胞质溶胶、线粒体和微粒体中的PLA2活性降低，抗PLC处理的心脏的微粒体中的PLC活性降低。此外，两种抗磷脂酶均减弱了肌酸激酶和乳酸脱氢酶向灌注液中的释放，并增加了再灌注心脏的收缩力以及冠状动脉血流量。本研究结果表明，PLA2和PLC均参与缺血心肌再灌注期间发生的磷脂降解和细胞损伤。
