Carloni Silvia, Mazzoni Erika, Cimino Mauro, De Simoni Maria Grazia, Perego Carlo, Scopa Claudia, Balduini Walter
Istituto di Farmacologia e Farmacognosia, Università degli Studi di Urbino Carlo Bo, Via S. Chiara 27, 61029 Urbino, Italy.
Neurobiol Dis. 2006 Jan;21(1):119-26. doi: 10.1016/j.nbd.2005.06.014. Epub 2005 Jul 27.
The present study was undertaken to evaluate whether in a neonatal model of stroke a prophylactic neuroprotective treatment with simvastatin modulates hypoxia-ischemia-induced inflammatory and apoptotic signaling. Procaspase-3 and cleaved caspase-3 expression showed a peak at 24 h and returned to control values after 5 days. Caspase-3 activity followed the same pattern of caspase-3 proteolytic cleavage. In simvastatin-treated ischemic animals, the expression of these proteins and caspase-3 activity were significantly lower when compared to that of ischemic animals. alpha-Spectrin and protein kinase C-alpha (PKCalpha) cleavages were not affected by the treatment. Poly (ADP-ribose) polymerase fragmentation, caspase-1 activation, and IL-1beta and ICAM-1 mRNA expression were increased by hypoxia-ischemia and significantly reduced in simvastatin-treated animals. The results indicate that simvastatin-induced attenuation of hypoxia-ischemia brain injury in the newborn rat occurs through reduction of the inflammatory response, caspase-3 activation, and apoptotic cell death.
本研究旨在评估在新生儿脑卒中模型中，用辛伐他汀进行预防性神经保护治疗是否能调节缺氧缺血诱导的炎症和凋亡信号。原半胱天冬酶 -3和裂解的半胱天冬酶 -3表达在24小时达到峰值，并在5天后恢复到对照值。半胱天冬酶 -3活性遵循与半胱天冬酶 -3蛋白水解切割相同的模式。在辛伐他汀治疗的缺血动物中，与缺血动物相比，这些蛋白的表达和半胱天冬酶 -3活性显著降低。α - 血影蛋白和蛋白激酶C -α（PKCα）的切割不受该治疗影响。缺氧缺血增加了聚（ADP - 核糖）聚合酶片段化、半胱天冬酶 -1激活以及白细胞介素 -1β和细胞间黏附分子 -1（ICAM -1）mRNA表达，而在辛伐他汀治疗的动物中显著降低。结果表明，辛伐他汀诱导的新生大鼠缺氧缺血性脑损伤减轻是通过减少炎症反应、半胱天冬酶 -3激活和凋亡细胞死亡实现的。
