Caspase-1抑制剂对小鼠蛛网膜下腔出血后早期继发性脑损伤的影响  

Effect of Ac-YVAD-CMK on early brain injury after subarachnoid hemorrhage in mice

作　　者：冯力[1] 李中林[1] 纪培志[1] 周波涛[1] 

机构地区：[1]徐州医学院附属医院神经外科,江苏徐州221002

出　　处：《中风与神经疾病杂志》2013年第12期1093-1095,共3页Journal of Apoplexy and Nervous Diseases

摘　　要：目的检测小鼠发生SAH后使用选择性IL-1β转换酶抑制剂是否能抑制活化IL-1β的生成、以及是否能减轻早期继发性脑损伤。方法通过血管内穿孔的方法制作SAH模型。112个小鼠分为对照组(n=22)、空白对照组(SAH+二甲亚砜DMSO,n=39)、低剂量组(SAH+Ac-YVAD-CMK,6mg/kg,n=28)和高剂量组(SAH+Ac-YVAD-CMK,10mg/kg,n=23)。药物在SAH发生后1h行腹腔内注射。早期继发性脑损伤通过24h内死亡率、24和72h的神经系统功能评分、脑组织含水量、伊文思蓝溢出实验和Western blot实验进行评估。结果虽然高低剂量组均可减弱成熟IL-1β的诱导产生,但只有高剂量(10mg/kg)治疗组能显著改善神经功能评分、死亡率、脑水肿和血脑屏障的破坏。结论 IL-1β的激活可能在SAH后的早期继发性脑损伤中扮演重要的角色。IL-1β转换酶抑制剂Ac-YVAD-CMK能有效地减轻SAH后的早期继发性脑损伤。Objective To examine the effects of Ac-YVAD-CMK （caspase-1 inhibitor） on generation of activated IL-1β and early brain injury （EBI） after subarachnoid hemorrhage（SAH）. Methods The endovascular perforation model of SAH was produced and 112 mice were assigned to sham, SAH vehicle, and SAH N-Ac-Tyr-Val-Ala-Asp-chloromethyl ke- tone （Ac-YVAD-CMK,6 and 10mg/kg） groups. Vehicle was administered intraperitoneally 1 hour post-SAH. EBI was as- sessed in terms of mortality within 24 hours, neurological scores, brain water content at 24 and 72 hours, Evans blue dye ex- travasation and Western blot for IL-1β at 24 hours after SAH. Results Both High-dose （10mg/kg） and low-dose （6mg/ kg） treatment group attenuated the mature IL-1β induction, but only High-dose （10mg/kg） treatment group significantly improved neurological scores, mortality, brain edema and damage of brain blood-brain barrier compared with the vehicle group. Conclusion IL-1β activation may play an important role in the pathogenesis of EBI after SAH. Ac-YVAD-CMK can significantly alleviate EBI after SAH.

关 键 词：蛛网膜下腔出血 早期脑损伤 白介素-1Β 脑水肿 

分 类 号：R743.35[医药卫生—神经病学与精神病学]