Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina 98100, Italy.
Neurosci Lett. 2011 Oct 3;503(2):93-9. doi: 10.1016/j.neulet.2011.08.015. Epub 2011 Aug 17.
Olprinone hydrochloride, a specific phosphodiesterase III inhibitor, has anti-inflammatory effects in addition to its inotropic and vasodilatory effects. The purpose of this study was to examine the beneficial effects of olprinone on cerebral ischemia reperfusion injury. In the present study, we examined the detailed mechanisms underlying the inhibitory effects of olprinone on inflammatory and apoptotic responses induced by middle cerebral artery occlusion (MCAo) in rats. Focal cerebral ischemia was induced by transient MCAo in the right hemisphere, via the external carotid artery into the internal carotid to block the origin of the median carotid artery. The rats were subjected to artery occlusion (2 h) followed by reperfusion (22 h). Olprinone was administered 5 min before reperfusion. MCAo-induced cerebral ischemia was associated with an increase in inducible nitric oxide synthase expression, nitrotyrosine formation, as well as IL-1β expression and ICAM-1 expression in ischemic regions. Olprinone treatment showed marked reduction in infarct size compared with control rats. These expressions were markedly inhibited by olprinone treatment. We also demonstrated that olprinone reduces levels of apoptosis (TUNEL, Bax and Bcl-2 expression) resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. Based on these findings we propose that olprinone would be useful in lowering the risk of damage or improving function in ischemia-reperfusion brain injury-related disorders.
盐酸奥普力农是一种特异性磷酸二酯酶 III 抑制剂，除了具有正性肌力作用和血管舒张作用外，还有抗炎作用。本研究旨在探讨奥普力农对脑缺血再灌注损伤的有益作用。在本研究中，我们研究了奥普力农抑制大鼠大脑中动脉闭塞（MCAo）诱导的炎症和细胞凋亡反应的详细机制。通过颈外动脉插入颈内动脉阻塞大脑中动脉来诱导右侧半脑的局灶性脑缺血，从而阻断大脑中动脉的起源。将大鼠进行动脉闭塞（2 h），然后再灌注（22 h）。奥普力农在再灌注前 5 分钟给予。MCAo 诱导的脑缺血与诱导型一氧化氮合酶表达增加、硝基酪氨酸形成以及缺血区 IL-1β表达和 ICAM-1 表达有关。与对照组大鼠相比，奥普力农治疗显著减少了梗死面积。奥普力农治疗明显抑制了这些表达。我们还表明，奥普力农降低了细胞凋亡水平（TUNEL、Bax 和 Bcl-2 表达），从而减少了缺血再灌注脑损伤中的梗死体积。基于这些发现，我们提出奥普力农可能有助于降低与缺血再灌注脑损伤相关疾病的损伤风险或改善功能。
