Therapeutic effect of caspase inhibitors in the prevention of apoptosis and reversal of chronic cerebral vasospasm
Therapeutic effect of caspase inhibitors in the prevention of apoptosis and reversal of chronic cerebral vasospasm
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DOI：
10.1054/jocn.2002.1088
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发表时间：
2002-11-01
影响因子：
2
通讯作者：
Zhang, JH
中科院分区：
文献类型：
--
作者：
Aoki, K;Zubkov, AY;Zhang, JH
蛛网膜下腔出血（SAH）后脑血管痉挛的重要组织学变化之一是内皮细胞损伤，其中涉及凋亡。目前的研究是为了确定抗凋亡治疗是否可以防止凋亡和逆转犬SAH模型中的血管痉挛。在第0天和第2天，将23只体重17- 25 kg的杂种犬（雌雄不限）自体动脉血注射到小脑延髓池中，并在第7天处死。在第0天血液注射前和第7天处死前进行血管造影。从第2天至第6天鞘内注射胱天蛋白酶-2（Z-VDVAD-FMK，10 μ M）抑制剂、胱天蛋白酶-3（Z-DEVD-FMK，10 μ M）抑制剂或载体（DMSO）。通过血管造影和透射电镜观察caspase抑制剂对细胞凋亡和血管痉挛的影响。未治疗的SAH犬第7天基底动脉的残余直径为第0天直径的53.4 +/- 5.5%。在这些动脉中观察到内皮细胞的显著损伤，包括凋亡样变化。这两种半胱天冬酶抑制剂都能防止内皮细胞的凋亡。然而，只有caspase-3抑制剂对减少13.3%的血管造影性血管痉挛具有接近显著的效果。更高的剂量和早期治疗，以及其他更有效的凋亡抑制剂，建议用于未来的研究。(C)2002爱思唯尔科技有限公司版权所有。
One of the important histological changes in cerebral vasospasm after subarachnoid hemorrhage (SAH) is endothelial cell damage, which involves apoptosis. The current study was undertaken to determine whether anti-apoptosis therapy prevents apoptosis and reverses vasospasm in a dog SAH model. Twenty-three mongrel dogs of either sex, weighing 17-25kg, were subjected to autologous arterial blood injection into the cisterna magna on day 0 and day 2, and sacrificed on day 7. Angiography was performed on day 0 before blood injection and on day 7 before sacrifice. Caspase-2 (Z-VDVAD-FMK, 10muM) inhibitor, caspase-3 (Z-DEVD-FMK, 10muM) inhibitor, or vehicle (DMSO) were injected intrathecally from day 2 to day 6. The effects of caspase inhibitors on apoptosis and vasospasm were evaluated by angiography and transmission electron microscopy. The residual diameter of the basilar artery on day 7 in SAH dogs without treatment was 53.4 +/- 5.5% of the day 0 diameter. Marked damage to the endothelial cells, including apoptotic like changes, was observed in these arteries. Both caspase inhibitors prevented apoptosis in the endothelial cells. Only caspase-3 inhibitor, however, had a near-significant effect on reducing 13.3% of angiographic vasospasm. Higher doses and early treatment, as well as other more potent apoptosis inhibitors, are recommended for future studies. (C) 2002 Elsevier Science Ltd. All rights reserved.