丁苯酞注射液对动脉瘤性蛛网膜下腔出血早期脑损伤的作用与机制探讨

doi:10.3969/j.issn.1673-5765.2018.07.011

摘要/Abstract

摘要：

目的探讨丁苯酞注射液对动脉瘤性蛛网膜下腔出血（aneurysmal subarachnoid hemorrhages，aSAH）患者早期脑损伤的作用与机制。

方法收集2017年8月-12月期间急性发病的aSAH患者66例，均在动脉瘤破裂后予以介入栓塞术治疗。入组患者随机分为观察组、对照组各33例。对照组术后常规药物及对症支持治疗，观察组在常规治疗的基础上加用丁苯酞注射液，100 ml，Q12 h，静脉滴注，两组病例均连续治疗7 d。分别于发病 1 d、3 d和7 d测定患者血清一氧化碳（nitric oxide，NO）、血清内皮素血管肽-1（endothelin-1，ET-1）、血清神经特异性烯醇酶（neuron specific enolase，NSE）、血清C反应蛋白（C-reactive protein，CRP）、血清细胞内黏附分子-1（intercellular adhesion molecule-1，ICAM-1）、血清白细胞介素-1β（Interleukin-1，IL-1β）的水平，并且在发病第4周记录两组患者迟发性脑梗死的发生情况，改良Rankin评分量表的评分。

结果观察组发病3 d、7 d的血清NO水平高于对照组，3 d、7 d血清ET-1、NSE、CRP、ICAM-1、IL-1β的水平低于对照组，差异均具有统计学意义。发病4周观察组改良Rankin评分量表≤2分的比例高于对照组，差异具有统计学意义。两组迟发性脑梗死发生无显著差异。

结论 aSAH后使用丁苯酞注射液能够降低与早期脑损伤相关的炎性因子水平，改善此类患者的预后。

文章导读： 本研究通过病例对照研究显示丁苯酞注射液可以减轻动脉瘤性蛛网膜下腔出血患者早期与脑损伤相关的炎症反应，从而改善早期预后。

关键词: 丁苯酞注射液; 动脉瘤; 蛛网膜下腔出血; 早期脑损伤

Abstract:

Objective To investigate the effect and mechanism of Butyphthalide injection on early brain injury in patients with aneurysmal subarachnoid hemorrhages (aSAH). Methods From August 2017 to December 2017, a total of 66 patients with acute aSAH were enrolled in the study. They were all treated by interventional embolization after aneurysm ruptured. They were randomly divided into observation group and control group, and 33 cases in each group. The control group received routine medication and symptomatic support treatment. The observation group was given intravenous Butyphthalide injection in addition, 100 ml, Q12 h. All the patients were treated continuously for 7 days. The levels of serum nitric oxide (NO), serum endothelin-1 (ET-1), serum neuron specific enolase (NSE), serum C reactive protein (CRP), serum intercellular adhesion molecule-1 (ICAM-1) and serum interleukin-1β (IL-1β) were determined on day 1, 3 and 7 after onset in both groups, and delayed cerebral infarction and modified Rankin scale (mRS) score were observed in all patients of two groups. Results The levels of NO in observation group were higher than that in control group on day 3 and 7, while the levels of ET-1, NSE, CRP, ICAM-1and IL-1β were all lower than that in control group on higher than that in control group, with statistical significance. There was no significant difference in delayed cerebral infarction incidence between two groups. Conclusion Using Butyphthalide after aSAH can reduce early brain injury, improve the prognosis of such patients. Decreasing inflammatory factors production using Butyphthalide may play a role on amelioration of focal brain injury.

Key words: Butyphthalide injection; Aneurysm, Subarachnoid hemorrhage, Early brain injury

刘昌亚, 胡学斌, 熊志勇, 郑津, 刘杨, 姚凡. 丁苯酞注射液对动脉瘤性蛛网膜下腔出血早期脑损伤的作用与机制探讨[J]. 中国卒中杂志, 2018, 13(07): 692-695.

LIU Chang-Ya, HU Xue-Bin, XIONG Zhi-Yong, ZHENG Jin, LIU Yang, YAO Fan. Effect and Mechanism of Butyphthalide Injection on Early Brain Injury in Aneurysmal Subarachnoid Hemorrhage[J]. Chinese Journal of Stroke, 2018, 13(07): 692-695.

参考文献

1] DHAR R，DIRINGER M. Statins and Anti-

Inflammatory Therapies for Subarachnoid

Hemorrhage[J]. Curr Treat Options Neurol，2012，14

（2）：164-174.

[2] JABBARLI R，REINHARD M，SHAH M，et al.

Early vasospasm after aneurysmal subarachnoid

hemorrhage predicts the occurrence and severity

of symptomatic vasospasm and delayed cerebral

ischemia[J]. Cerebrovasc Dis，2016，41（5-6）：265-

272.

[3] CHOI H A，BAJGUR S S，JONES W H，et al.

Quantification of cerebral edema after subarachnoid

hemorrhage[J]. Neurocritical Care，2016，25（1）：

64-70.

[4] LE ROUX A A，WALLACE M C. Outcome and

cost of aneurysmal subarachnoid hemorrhage[J].

Neurosurg Clin N Am，2010，21（2）：235-246.

[5] PLUTA R M，HANSEN-SCHWARTZ J，DREIER

J，et al. Cerebral vasospasm following subarachnoid

hemorrhage：time for a new world of thought[J].

Neurol Res，2009，31（2）：151-158.

[6] SEHBA F A，PLUTA R M，ZHANG J H.

Metamorphosis of subarachnoid hemorrhage research：

from delayed vasospasm to early brain injury[J]. Mol

Neurobiol，2011，43（1）：27-40.

[7] JUVELA S. Plasma endothelin concentrations

after aneurysmal subarachnoid hemorrhage[J]. J

Neurosurg，2000，92（3）：390-400.

[8] OSTROWSKI R P，COLOHAN A R，ZHANG J H.

Molecular mechanisms of early brain injury after

subarachnoid hemorrhage[J]. Neurol Res，2006，28

（4）：399-414.

[9] BRANDNER S，THALER C，BUCHFELDER M，

et al. Brain-derived protein concentrations in the

cerebrospinal fluid：contribution of trauma resulting

from ventricular drain insertion[J]. J Neurotrauma，

2013，30（13）：1205-1210.

[10] BELLAPART J，JONES L，BANDESHE H，et al.

Plasma endothelin-1 as screening marker for cerebral

vasospasm after subarachnoid hemorrhage[J].

Neurocrit Care，2014，20（1）：77-83.

[11] AL-MUFTI F，AMULURU K，SMITH B，et

al. Early Emerging Markers Of Delayed Cerebral

Ischemia Following Aneurysmal Subarachnoid

Hemorrhage：A Literature Review[J/OL]. World

Neurosurg，2017，107：148-159. https：//doi.

org/10.1016/j.wneu.2017.07.114.

[12] SRINIVASAN A，AGGARWAL A，GAUDIHALLI

S，et al. Impact of early leukocytosis and elevated

high-sensitivity c-reactive protein on delayed

cerebral ischemia and neurologic outcome

after subarachnoid hemorrhage[J/OL]. World

Neurosurg，2016，90：91-95. https：//doi.org/10.1016/

j.wneu.2016.02.049.

[13] GALEA J，OGUNGBENRO K，HULME S，et

al. Reduction of inflammation after administration

of interleukin-1 receptor antagonist following

aneurysmal subarachnoid hemorrhage：results of the

Subcutaneous Interleukin-1Ra in SAH（SCIL-SAH）

study[J]. J Neurosurg，2018，128（2）：515-523.

[1]	程实, 李静, 郭军平, 胡爱香, 于鑫玮, 韩玮, 梁瑛, 张越巍, 冀瑞俊. 急性卒中患者住院期间感染的临床特征及危险因素分析[J]. 中国卒中杂志, 2022, 17(10): 1065-1070.
[2]	王李, 李振水, 吴俊, 许英霞, 郝春满. 接受围手术期标准加速康复管理的颅内动脉瘤患者营养状态与显微外科夹闭术后并发症关系研究[J]. 中国卒中杂志, 2022, 17(09): 966-971.
[3]	吴倩, 陶立元, 陈思琪, 钟莲梅, 刘丽萍, 米东华. 血糖波动对动脉瘤性蛛网膜下腔出血后迟发性脑缺血及30天死亡的影响 [J]. 中国卒中杂志, 2022, 17(08): 845-850.
[4]	宋绪林, 陈来照, 韦明桂. 大脑前动脉A2段构型对左侧翼点入路夹闭前交通动脉瘤的影响 [J]. 中国卒中杂志, 2022, 17(08): 851-856.
[5]	王拥军, 李子孝, 谷鸿秋, 翟屹, 姜勇, 周齐, 赵性泉, 王伊龙, 杨昕, 王春娟, 孟霞, 李昊, 刘丽萍, 荆京, 吴静, 徐安定, 董强, David Wang, 王文志, 马旭东, 赵继宗, 《中国卒中报告》编写委员会（第一作者）. 中国卒中报告2020（中文版）（3）[J]. 中国卒中杂志, 2022, 17(07): 675-682.
[6]	王拥军, 李子孝, 谷鸿秋, 翟屹, 姜勇, 周齐, 赵性泉, 王伊龙, 杨昕, 王春娟, 孟霞, 李昊, 刘丽萍, 荆京, 吴静, 徐安定, 董强, David Wang, 王文志, 马旭东, 赵继宗, 《中国卒中报告》编写委员会（第一作者）. 中国卒中报告2020（中文版）（2）[J]. 中国卒中杂志, 2022, 17(06): 553-567.
[7]	王拥军, 李子孝, 谷鸿秋, 翟屹, 姜勇, 周齐, 赵性泉, 王伊龙, 杨昕, 王春娟, 孟霞, 李昊, 刘丽萍, 荆京, 吴静, 徐安定, 董强, David Wang, 王文志, 马旭东, 赵继宗, 《中国卒中报告》编写委员会（第一作者）. 中国卒中报告2020（中文版）（1）[J]. 中国卒中杂志, 2022, 17(05): 433-447.
[8]	邓子茹, 孙文, 陈育华, 吕心怡, 桂韦. 缘于未破裂颅内囊状动脉瘤的头痛研究进展[J]. 中国卒中杂志, 2022, 17(05): 472-476.
[9]	张霞, 余正阳, 于丹丹, 田德财, 杨中华, 刘丽萍. 2例小脑幕区硬脑膜动静脉瘘误诊病例报告[J]. 中国卒中杂志, 2022, 17(04): 398-401.
[10]	杨卜凡, 邹新宇, 龚小沉, 都泓材, 陈忠伦, 唐宇凤, 李肇坤. 反应性红细胞增多症伴大脑前动脉夹层动脉瘤致脑梗死1例[J]. 中国卒中杂志, 2022, 17(03): 310-313.
[11]	鲁悦, 陶涛, 庄宗, 李伟, 杭春华. 以问题为基础教学法在颅内动脉瘤外科治疗临床教学中的应用[J]. 中国卒中杂志, 2021, 16(12): 1302-1304.
[12]	郭加欢, 赵性泉. 蛛网膜下腔出血后迟发性脑缺血的病理生理机制探讨[J]. 中国卒中杂志, 2021, 16(07): 746-751.
[13]	张永智, 刘彬冰, 田杨, 史怀璋. 线粒体自噬在蛛网膜下腔出血中的研究进展[J]. 中国卒中杂志, 2021, 16(07): 752-756.
[14]	曹毅. 支架辅助栓塞在颅内动脉瘤治疗中的应用[J]. 中国卒中杂志, 2021, 16(06): 533-536.
[15]	胡航, 曹毅, 鲍娟. 血流导向装置治疗颅内大型或巨大型动脉瘤的研究进展[J]. 中国卒中杂志, 2021, 16(06): 538-543.