Anderson K E, Du X J, Sinclair A J, Woodcock E A, Dart A M
Cellular Biochemistry Laboratory, Baker Medical Research Institute, Prahran, Australia.
Am J Physiol. 1996 Oct;271(4 Pt 2):H1483-90. doi: 10.1152/ajpheart.1996.271.4.H1483.
Dietary enrichment with fish oil-derived n-3 polyunsaturated fatty acids has been shown to suppress the arrhythmias that occur during postischemic reperfusion. We have recently implicated a rapid release of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] during postischemic reperfusion in the generation of these arrhythmias. The effects of dietary supplementation with fish oil on both cardiac Ins(1,4,5)P3 and arrhythmogenic responses to reperfusion were therefore investigated in perfused rat hearts. Comparisons were made with control and n-6 polyunsaturated or saturated fat-supplemented diets. In control hearts, reperfusion increased Ins(1,4,5)P3 levels [from 9 +/- 2 at 20 min ischemia to 26 +/- 3 counts per minute (cpm)/mg protein with 2 min of reperfusion] and produced a high incidence of ventricular tachycardia (92% VT) and ventricular fibrillation (85% VF). Dietary fish oil supplementation, which increased composition of n-3 fatty acids in myocardial membrane phospholipids, prevented the reperfusion-induced rise in Ins(1,4,5)P3 (11 +/- 1 at 20 min ischemia and 12 +/- 2 cpm/mg protein after 2-min reperfusion) and significantly suppressed reperfusion arrhythmias (38% VT, 13% VF; P < 0.01 vs. control group). Thus the inhibition of reperfusion-induced rises in Ins(1,4,5)P3 by n-3 polyunsaturated fatty acids after dietary fish oil supplementation provides a possible mechanism for the inhibitory effect of n-3 fatty acids on reperfusion-induced arrhythmias.
饮食中富含鱼油来源的n-3多不饱和脂肪酸已被证明可抑制缺血后再灌注期间发生的心律失常。我们最近发现，缺血后再灌注期间D-肌醇1,4,5-三磷酸[Ins(1,4,5)P3]的快速释放与这些心律失常的发生有关。因此，我们在灌注的大鼠心脏中研究了饮食补充鱼油对心脏Ins(1,4,5)P3以及对再灌注致心律失常反应的影响。并与对照组以及补充n-6多不饱和脂肪酸或饱和脂肪的饮食进行了比较。在对照心脏中，再灌注会增加Ins(1,4,5)P3水平[从缺血20分钟时的9±2增加到再灌注2分钟时的26±3计数每分钟（cpm）/毫克蛋白质]，并产生高发生率的室性心动过速（92% VT）和室颤（85% VF）。饮食中补充鱼油可增加心肌膜磷脂中n-3脂肪酸的组成，可防止再灌注引起的Ins(1,4,5)P3升高（缺血20分钟时为11±1，再灌注2分钟后为12±2 cpm/毫克蛋白质），并显著抑制再灌注心律失常（38% VT，13% VF；与对照组相比P < 0.01）。因此，饮食补充鱼油后n-3多不饱和脂肪酸对再灌注引起的Ins(1,4,5)P3升高的抑制作用为n-3脂肪酸对再灌注诱导的心律失常的抑制作用提供了一种可能的机制。
