Huang J Q, Radinovic S, Rezaiefar P, Black S C
Merck Frosst Canada, P.O. Box 1005, Dorval, Pointe-Claire, QC H9R 4P8, Canada.
Eur J Pharmacol. 2000 Aug 18;402(1-2):139-42. doi: 10.1016/s0014-2999(00)00477-5.
The aim of this study was to determine the effect of different administration protocols on the cardioprotective efficacy of the non-selective, irreversible caspase inhibitors N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) and bocaspartyl-(OMe)-fluoromethylketone (BocD.fmk) in a rat in vivo ischemia and reperfusion paradigm. Hearts were made ischemic for 45 min and reperfused for 180 min. Under these conditions, it was determined that zVAD.fmk was cardioprotective when administered before or after the onset of ischemia, whereas BocD.fmk was efficacious only when administered before the onset of ischemia. This is the first report of in vivo cardioprotection by a caspase inhibitor when administered after the onset of ischemia.
本研究的目的是在大鼠体内缺血再灌注模型中，确定不同给药方案对非选择性、不可逆半胱天冬酶抑制剂N-苄氧羰基-Val-Ala-Asp-氟甲基酮（zVAD.fmk）和叔丁氧羰基天冬氨酸-(OMe)-氟甲基酮（BocD.fmk）心脏保护功效的影响。心脏缺血45分钟，再灌注180分钟。在这些条件下，已确定zVAD.fmk在缺血发作前或发作后给药时具有心脏保护作用，而BocD.fmk仅在缺血发作前给药时有效。这是首次关于半胱天冬酶抑制剂在缺血发作后给药具有体内心脏保护作用的报道。
