罗格列酮对家兔脑出血模型病灶周围内皮素-1表达及血脑屏障通透性的影响

摘要

目的:探讨罗格列酮对家兔脑出血(ICH)模型血肿周围脑组织内皮素1(ET-1)表达及血脑屏障通透性的影响.方法:45只健康家兔随机分为正常对照组(NC组)、模型对照组(MC组)及罗格列酮灌注组(RSG组),各15只.自体血注入法制备基底核区ICH模型.造模后6 h,RSG组给予罗格列酮病灶区灌注,各组分别在处理后1、3和7 d处死,每时间点5只.处死前行Purdy神经功能评分,伊文思蓝法判断血脑屏障通透性,比较血肿周围脑组织ET-1表达,分析ET-1表达水平与血肿周围脑组织伊文思蓝含量及Purdy神经功能评分相关性.结果:与NC组比较,MC组和RSG组出现显著神经功能损害(P<0.05),病灶周围ET-1表达、血脑屏障通透性均显著增加(P<0.05);与MC组比较,RSG组神经功能损害减轻,病灶周围ET-1表达、血脑屏障通透性均降低(P<0.05);血肿周围脑组织ET-1表达水平与血脑屏障通透性及Purdy神经功能评分呈显著相关性(P<0.01).结论:ICH后血肿周围脑组织ET-1表达及血脑屏障通透性增加,罗格列酮灌注治疗可降低血肿周围脑组织ET-1表达及血脑屏障通透性,减轻神经功能损害.%Objective: To investigate the effect of rosiglitazone on perihematomal brain tissue endothelin-1 (ET-1) expression and blood-brain barrier permeability in rabbits with intracerebral hemorrhage (ICH). Methods: Forty-five healthy rabbits were randomly divided into a normal control group (NC group), model control group (MC group), and rosiglitazone perfusion group (RSG group), with 15 rabbits per group. Autologous blood injection was used to establish basal ganglia ICH model. Six hours after generating model, rabbits in the RSG group were given a rosiglitazone perfusion to the lesion site. Each group was divided into three subgroups (5 rabbits per subgroup), and animals in each subgroup were euthanized on days 1, 3, and 7 post-procedure. Before euthanasia, neurological deficit scores (Purdy scores) were determined and Evans blue staining was performed to determine blood-brain barrier permeability. After rabbits were sacrificed, perihematomal brain tissue was removed to determine ET-1 expression. Data was analyzed for correlation between ET-1 expression levels and Evans blue stained perihematomal brain tissue and Purdy scores.Results:In MC and RSG groups,significant neurological impairment was found(P<0.05),and ET-1 expression and BBB permeability surrounding the lesion site were significantly increased compared to the NC group(P<0.05).When compared to the MC group, the RSG group showed a decrease in neurological impairment, ET-1 expression surrounding the lesion,and BBB permeability(P<0.05).ET-1 expression in perihematomal brain tissue showed significant correlation with blood-brain barrier permeability and Purdy neurological deficit scores (P<0.01). Conclusion:ET-1 expression in perihematomal brain tissue and blood-brain barrier permeability increased after intracerebral hemorrhage. RSG infusion therapy can reduce the expression of ET-1 in brain tissue around hematomas and decrease the permeability of the blood-brain barrier,thereby reducing neurological damage.