Déry Marc-André, Rousseau Guy, Benderdour Mohamed, Beaumont Eric
Centre de recherche, Hôpital du Sacré-Coeur de Montréal, Département de pharmacologie, Université de Montréal, Montréal, Québec, Canada.
Neurosci Lett. 2009 Mar 27;453(1):73-6. doi: 10.1016/j.neulet.2009.01.062. Epub 2009 Jan 29.
The systemic administration of atorvastatin has been shown to be neuroprotective after spinal cord injury (SCI), by decreasing the inflammatory response at the lesion site and by reducing neuronal and oligodendrocyte apoptosis. The latter effect spares white matter at the injury site and improves locomotion. The aim of this study was to confirm the neuroprotective efficacy of atorvastatin as well as its early action in limiting apoptosis with its administration post-SCI. Female Sprague-Dawley rats received an intra peritoneal injection of: (1) statin/saline (5mg/kg) at 2h after the contusion injury; (2) physiological saline at 2h post-SCI; or (3) physiological saline without injury. Statin-treated rats showed significant (p<0.05) improvement in locomotion at week 4 post-SCI compared to vehicle-treated animals. Explaining this outcome, caspase-3 activity decreased by 50% (p<0.05), and the histological TUNEL method revealed a decrease of approximately 20% in apoptotic cells at the injury site (p<0.01) at 4h post-SCI in atorvastatin-treated rats in comparison to vehicle-treated controls. These data demonstrate that atorvastatin is effective after experimental spinal cord contusion injury in preventing early apoptosis at the injury site within 2h post-administration.
已证明，阿托伐他汀全身给药在脊髓损伤（SCI）后具有神经保护作用，其机制是减少损伤部位的炎症反应以及减少神经元和少突胶质细胞的凋亡。后一种作用可使损伤部位的白质免受损伤，并改善运动功能。本研究的目的是证实阿托伐他汀的神经保护作用及其在SCI后给药对限制凋亡的早期作用。雌性Sprague-Dawley大鼠接受腹腔注射：（1）在挫伤性损伤后2小时注射他汀类药物/生理盐水（5mg/kg）；（2）SCI后2小时注射生理盐水；或（3）未受伤情况下注射生理盐水。与接受载体处理的动物相比，接受他汀类药物治疗的大鼠在SCI后第4周运动功能有显著改善（p<0.05）。对此结果的解释是，与接受载体处理的对照组相比，阿托伐他汀治疗的大鼠在SCI后4小时，半胱天冬酶-3活性降低了50%（p<0.05），组织学TUNEL法显示损伤部位凋亡细胞减少了约20%（p<0.01）。这些数据表明，阿托伐他汀在实验性脊髓挫伤性损伤后给药2小时内可有效预防损伤部位的早期凋亡。
