RCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy.
Eur J Pharmacol. 2011 Jan 15;650(2-3):612-20. doi: 10.1016/j.ejphar.2010.10.043. Epub 2010 Oct 27.
Coronary ischemia and subsequent reperfusion result in deleterious effects, one of the principal ones being vascular and myocardial inflammation. Olprinone hydrochloride, a specific phosphodiesterase III inhibitor, has anti-inflammatory effects in addition to its inotropic and vasodilator effects. The purpose of this study was to examine the beneficial effects of olprinone on myocardial ischemia-reperfusion injury. Myocardial ischemia-reperfusion injury was caused by clamping the LAD (left anterior descending) coronary artery for 25 min followed by a release of the clamp allowing reperfusion for 1 h. Olprinone i.p. (0.2 mg/kg, i.p.) was administrated 15 min after ischemia. The olprinone administration significantly reduced the: (1) histological evidence of myocardial injury, (2) pro-inflammatory cytokines: tumor necrosis factor-α (TNF-α) and Interleukin-1β (IL-1β), (3) adhesion molecules: Inter-Cellular Adhesion Molecule 1 (ICAM-1) and P-Selectin, (4) nitrotyrosine formation, (5) nuclear factor kappa-B (NF-κB) expression, (6) Poly (ADP-ribose) (PAR) formation, and (7) apoptosis (Bax, Bcl-2, Fas-L and terminal deoxynucleotidyl transferase-mediated UTP end labeling (TUNEL). Based on these findings this study provides the evidence that treatment with olprinone ameliorated the inflammatory process associated with myocardial ischemia-reperfusion in rats and suggests that this drug may have potential in the treatment of various ischemia and reperfusion diseases.
冠状动脉缺血及随后的再灌注会产生有害作用，其中主要的作用之一是血管和心肌炎症。盐酸奥普力农是一种特异性磷酸二酯酶 III 抑制剂，除了具有正性肌力和血管扩张作用外，还有抗炎作用。本研究旨在探讨奥普力农对心肌缺血再灌注损伤的有益作用。心肌缺血再灌注损伤是通过夹闭 LAD（左前降支）冠状动脉 25 分钟，然后松开夹子允许再灌注 1 小时来造成的。奥普力农（0.2mg/kg，ip）在缺血后 15 分钟腹腔内给药。奥普力农给药显著减少：（1）心肌损伤的组织学证据，（2）促炎细胞因子：肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β），（3）粘附分子：细胞间粘附分子 1（ICAM-1）和 P 选择素，（4）硝基酪氨酸形成，（5）核因子 kappa-B（NF-κB）表达，（6）多聚（ADP-核糖）（PAR）形成，和（7）细胞凋亡（Bax、Bcl-2、Fas-L 和末端脱氧核苷酸转移酶介导的 UTP 末端标记（TUNEL）。基于这些发现，本研究提供了证据，表明奥普力农治疗改善了与大鼠心肌缺血再灌注相关的炎症过程，并表明该药物可能在各种缺血和再灌注疾病的治疗中有潜力。
