丙酮酸乙酯对蛛网膜下腔出血后延迟性脑血管痉挛的治疗作用及机制  

Effect and mechanism of ethyl pyruvate on delayed cerebral vasospasm after subarachnoid hemorrhage

作　　者：金珂[1] 金义超[1] 吕涛[1] 张封臣 张晓华[1] 

机构地区：[1]上海交通大学医学院附属仁济医院神经外科,上海200127

出　　处：《上海交通大学学报（医学版）》2017年第12期1601-1607,共7页Journal of Shanghai Jiao tong University:Medical Science

基　　金：国家自然科学基金(81471333)~~

摘　　要：目的·观察大鼠蛛网膜下腔出血(SAH)后不同时期脑血管痉挛(CVS)程度,研究丙酮酸乙酯(EP)对SAH后CVS的缓解作用及机制。方法·将50只健康SD大鼠随机分为假手术组、SAH 3日组、SAH 5日组、SAH 7日组、SAH 9日组(每组n=10)。假手术组行小脑延髓池2次注入0.3 m L生理盐水,SAH组行小脑延髓池2次注入自体血0.3 m L致延迟性CVS,观察各组的神经功能情况及CVS程度。另取48只健康SD大鼠随机分为假手术+生理盐水(等体积)组、SAH+生理盐水(等体积)组、SAH+EP[100 mg/(kg·d)]组(每组n=16)。观察在第7日各组的神经功能情况、CVS程度、基底动脉血管壁细胞凋亡水平,及p-Akt、Bax、Bcl-2、cleaved caspase-3的表达量。结果·SAH组大鼠在第3日出现明显的CVS,第5日有所缓解,第7日CVS达到峰值,第9日CVS逐渐缓解。第7日时相对于假手术+生理盐水组,SAH+生理盐水组出现明显神经功能缺失症状,基底动脉管壁明显痉挛,血管壁细胞凋亡显著,Bax及cleaved caspase-3的表达量明显上调,p-Akt及Bcl-2的表达量明显下调;第7日时相对于SAH+生理盐水组,SAH+EP组神经功能明显改善,CVS明显缓解,基底动脉血管壁细胞凋亡明显减少,Bax及caspase-3的表达量明显下调,p-Akt及Bcl-2的表达量明显上调。结论·大鼠小脑延髓池二次注血模型在第7日时CVS最严重。EP对SAH后延迟性CVS有缓解作用,其机制可能与抑制细胞凋亡有关。PI3K/Akt信号通路可能参与其中,有望为脑血管痉挛提供新的治疗靶点。Objective·To observe the degree of cerebral vasospasm （CVS） after subarachnoid hemorrhage （SAH） at different time points, and to investigate the effects of ethyl pyruvate （EP） on CVS following SAH and its mechanism. Methods·Fifty healthy SD rats were randomly divided into five groups i.e. sham group, SAH-3 d group, SAH-5 d group, SAH-7 d group and SAH-9 d group （n=10 in each group）. Sham group was built by double cisternal injection with 0.3 mL saline each time, and SAH group was built by double cisternal injection with 0.3 mL autologous blood each time. The neurological function and degree of CVS were observed. Another forty-eight healthy SD rats were randomly divided into three groups i.e. sham＋saline （equal volume） group, SAH＋saline （equal volume） group and SAH＋EP [100 mg/（kg·d）] group （n=16 in each group）. The neurological function, degree of CVS and cell apoptosis of basilar artery were observed on day 7. The expressions of p-Akt, Bax, Bcl-2 and cleaved caspase-3 were also observed on day 7. Results·CVS significantly increased on day 3, decreased on day 5, and then significantly increased to top level on day 7, and gradually decreased on day 9. Compared with sham＋saline group, the neurological scores were significantly decreased in SAH＋saline group on day 7. Compared with sham＋saline group, CVS and cell apoptosis of basilar artery were significantly increased in SAH＋saline group on day 7. Compared with sham＋saline group, the expressions of Bax and cleaved caspase-3 were significantly up-regulated, while the expressions of p-Akt and Bcl-2 were significantly down-regulated in SAH＋saline group on day 7. Compared with SAH＋saline group, the neurological scores significantly increased in SAH＋EP group on day 7. Compared with SAH＋saline group, CVS and cell apoptosis of basilar artery significantly decreased in SAH＋EP group on day 7. Compared with SAH＋saline group, the expressions of Bax and cleaved caspase-3 were significantly down-regulated, while the

关 键 词：丙酮酸乙酯 蛛网膜下腔出血 脑血管痉挛 细胞凋亡 

分 类 号：R743.35[医药卫生—神经病学与精神病学]