上海交通大学学报(医学版) ›› 2017, Vol. 37 ›› Issue (12): 1601-.doi: 10.3969/j.issn.1674-8115.2017.12.004

• 论著(基础研究) • 上一篇    下一篇

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

金珂,金义超,吕涛,张封臣,张晓华   

  1. 上海交通大学医学院附属仁济医院神经外科,上海 200127
  • 出版日期:2017-12-28 发布日期:2018-01-10
  • 通讯作者: 张晓华,电子信箱:zxh1969@aliyun.com。
  • 作者简介:金 珂(1991—),男,硕士生;电子信箱:runningkiing@163.com。
  • 基金资助:
     国家自然科学基金(81471333)

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

JIN Ke, JIN Yi-chao, Lü Tao, ZHANG Feng-chen, ZHANG Xiao-hua #br#   

  1. Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • Online:2017-12-28 Published:2018-01-10
  • Supported by:
    National Natural Science Foundation of China, 81471333

摘要: [ 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 mL 生理盐水,SAH 组行小脑延髓池 2 次注入自体血 0.3 mL 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。

关键词: 丙酮酸乙酯, 蛛网膜下腔出血, 脑血管痉挛, 细胞凋亡

Abstract: [Abstract] Objective · To observe the degree of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) at different time poininvestigate the effects of ethyl pyruvate (EP) on CVS following SAH and its mechanism. Methods · Fifty healthy SD rats were randomly difive 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 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 neurological function and degree of CVS were observed. Another forty-eight healthy SD rats were randomly divided into three groups i.e. sh(equal volume) group, SAH+saline (equal volume) group and SAH+EP [100 mg/(kg·d)] group (n=16 in each group). The neurological functionCVS 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 Results · CVS significantly increased on day 3, decreased on day 5, and then significantly increased to top level on day 7, and gradually decreased Compared with sham+saline group, the neurological scores were significantly decreased in SAH+saline group on day 7. Compared with sham+saCVS and cell apoptosis of basilar artery were significantly increased in SAH+saline group on day 7. Compared with sham+saline group, the eof Bax and cleaved caspase-3 were significantly up-regulated, while the expressions of p-Akt and Bcl-2 were significantly down-regulated in SAgroup on day 7. Compared with SAH+saline group, the neurological scores significantly increased in SAH+EP group on day 7. Compared with Sgroup, CVS and cell apoptosis of basilar artery significantly decreased in SAH+EP group on day 7. Compared with SAH+saline group, the exprBax and cleaved caspase-3 were significantly down-regulated, while the expressions of p-Akt and Bcl-2 were significantly up-regulated in SAH+EP day 7. Conclusion · The double hemorrhage model rat has most severely CVS on day 7. EP can attenuate vasospasm after SAH, and its mechanisassociated with inhibition of cell apoptosis. PI3K/Akt signaling pathway may be involved, which may provide a novel therapeutic target for CVS.

Key words: ethyl pyruvate, subarachnoid hemorrhage, cerebral vasospasm, cell apoptosis