Department of Pharmacology, University of Melbourne, Parkville, VIC, Australia.
Free Radic Biol Med. 2011 Oct 1;51(7):1437-44. doi: 10.1016/j.freeradbiomed.2011.07.003. Epub 2011 Jul 18.
The mechanism of flavonol-induced cardioprotection is unclear. We compared the protective actions of a flavonol that inhibits calcium utilization and has antioxidant activity, 3',4'-dihydroxyflavonol (DiOHF); a flavonol that affects only calcium activity, 4'-OH-3'-OCH(3)-flavonol (4'-OH-3'-OCH(3)F); and a water-soluble flavonol with selective antioxidant activity, DiOHF-6-succinamic acid (DiOHF-6-SA), in isolated, perfused rat hearts. Hearts were subjected to global ischemia for 20 min followed by 30 min reperfusion and were treated with vehicle (0.05% DMSO), DiOHF, 4'-OH-3'-OCH(3)F, or DiOHF-6-SA (all 10 μM, n=5-8 per group). Flavonols were infused for 10 min before ischemia and during reperfusion. In vehicle-treated hearts, left-ventricular (LV) +dP/dt was reduced by 60% at the end of reperfusion compared to the preischemic level. Lactate dehydrogenase (LDH) release was elevated and endothelial NO synthase (eNOS) expression was lower in vehicle-treated hearts compared to shams. In comparison, DiOHF treatment improved LV function upon reperfusion, decreased LDH, and preserved eNOS expression. The antioxidant DiOHF-6-SA also preserved contractility, reduced LDH, and preserved eNOS expression. In contrast, hearts treated with 4'-OH-3'-OCH(3)F showed a degree of contractile impairment similar to that of the vehicle group. DiOHF and DiOHF-6-SA also exerted cardioprotection when given only during reperfusion and not when administered only before ischemia. Flavonol-induced cardioprotection relies on antioxidant activity and is mainly exerted during reperfusion.
黄酮醇诱导的心脏保护作用的机制尚不清楚。我们比较了一种黄酮醇，它抑制钙利用并具有抗氧化活性，3'，4'-二羟基黄酮醇（DiOHF）；一种仅影响钙活性的黄酮醇，4'-羟基-3'-OCH（3）-黄酮醇（4'-OH-3'-OCH（3）F）；以及一种具有选择性抗氧化活性的水溶性黄酮醇，3'，4'-二羟基黄酮醇-6-琥珀酸（DiOHF-6-SA），在分离的灌注大鼠心脏中。心脏经历 20 分钟的整体缺血，然后进行 30 分钟的再灌注，并给予载体（0.05%DMSO）、DiOHF、4'-OH-3'-OCH（3）F 或 DiOHF-6-SA（均为 10μM，每组 5-8 只）。黄酮醇在缺血前 10 分钟和再灌注期间输注。在载体处理的心脏中，与缺血前水平相比，左心室（LV）+dP/dt 在再灌注结束时降低了 60%。与假手术相比，载体处理的心脏中乳酸脱氢酶（LDH）释放增加，内皮型一氧化氮合酶（eNOS）表达降低。相比之下，DiOHF 治疗可改善再灌注时的 LV 功能，降低 LDH，并维持 eNOS 表达。抗氧化剂 DiOHF-6-SA 也可维持收缩功能，降低 LDH，并维持 eNOS 表达。相比之下，用 4'-OH-3'-OCH（3）F 处理的心脏显示出与载体组相似的收缩功能障碍程度。DiOHF 和 DiOHF-6-SA 仅在再灌注期间给药而不在缺血前给药时也发挥心脏保护作用。黄酮醇诱导的心脏保护作用依赖于抗氧化活性，主要在再灌注期间发挥作用。
