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Advances in Clinical Medicine
Vol. 13  No. 03 ( 2023 ), Article ID: 63582 , 7 pages
10.12677/ACM.2023.133716

丁苯酞联合阿替普酶对急性脑梗死患者静脉溶栓后神经功能缺损严重程度临床疗效观察

胡月圆1，车峰远2*

1锦州医科大学临沂市人民医院研究生培养基地，山东 临沂

2山东省临沂市人民医院神经内科，山东 临沂

收稿日期：2023年2月27日；录用日期：2023年3月23日；发布日期：2023年3月31日

摘要

目的：探讨丁苯酞联合阿替普酶对急性脑梗死患者静脉溶栓后神经功能缺损严重程度及预后的影响。方法：根据入排标准选取临沂市人民医院神经内科住院治疗的首次急性脑梗死患者200例，实验组给予阿替普酶联合丁苯酞治疗，对照组给予阿替普酶治疗，按照美国国立卫生院卒中量表(NIHSS)评定患者入院时、溶栓后24 h、溶栓后7 d及出院时的NIHSS评分；记录患者入院期间的不良事件(牙龈出血、鼻出血、消化道出血、脑出血、进展性卒中等)；90天随访中按照改良的Rankin (mRS)评分量表记录患者预后情况(mRS ≤ 2分预后良，mRS > 2分预后不良)。比较各组间的差异，分析丁苯酞联合阿替普酶对急性脑梗死患者静脉溶栓后神经功能缺损严重程度及预后的影响。结果：两组患者一般临床资料、生化指标、入院时NIHSS评分及溶栓后24 h NIHSS评分相比较，差异均无统计学意义(P > 0.05)；实验组患者溶栓后7 d及出院时的NIHSS评分均低于对照组，差异有统计学意义(P < 0.05)；随访90天，实验组预后不良发生率低于对照组，差异有统计学意义(P < 0.05)；实验组不良事件发生率高于对照组，差异无统计学意义(P > 0.05)。结论：丁苯酞联合阿替普酶能显著改善急性脑梗死患者神经功能缺损程度及预后，且安全性较高。

关键词

丁苯酞，阿替普酶，急性脑梗死，神经功能缺损，预后

Clinical Efficacy Observation of Butylphthalide Combined with Alteplase on the Severity of Neurological Deficit in Patients with Acute Cerebral Infarction after Intravenous Thrombolysis

Yueyuan Hu1, Fengyuan Che2*

1Graduate Training Base, Linyi People’s Hospital, Jinzhou Medical University, Linyi Shandong

2Department of Neurology, Linyi People’s Hospital, Linyi Shandong

Received: Feb. 27th, 2023; accepted: Mar. 23rd, 2023; published: Mar. 31st, 2023

ABSTRACT

Objective: To investigate the effect of butylphthalide combined with alteplase on the severity and prognosis of neurological deficit in patients with acute cerebral infarction after intravenous thrombolysis. Methods: A total of 200 patients with first acute cerebral infarction who were hospitalized in the Department of Neurology, Linyi People’s Hospital were selected according to the admission and exclusion criteria. The experimental group was treated with alteplase combined with butylphthalide, and the control group was treated with alteplase. The NIHSS scale (NIHSS) was used to assess the NIHSS score of patients at admission, 24 hours after thrombolysis, 7 days after thrombolysis and at discharge; adverse events (gingival bleeding, epistaxis, gastrointestinal bleeding, cerebral hemorrhage, progressive stroke) were recorded during admission. The prognosis of patients was recorded according to the modified Rankin (mRS) score during the 90-day follow-up (mRS ≤ 2 points, good prognosis, mRS > 2 points, poor prognosis). The differences between the groups were compared, and the effect of butylphthalide combined with alteplase on the severity and prognosis of neurological deficit in patients with acute cerebral infarction after intravenous thrombolysis was analyzed. Results: There was no significant difference in general clinical data, biochemical indexes, NIHSS score at admission and NIHSS score 24 hours after thrombolysis between the two groups (P > 0.05). The NIHSS scores of patients in the experimental group were lower than those in the control group 7 days after thrombolysis and at discharge, compared with the control group, the difference was statistically significant (P < 0.05); after 90 days of follow-up, the incidence of poor prognosis in the treatment group was lower than that in the control group, and the difference was statistically significant (P < 0.05); the incidence of adverse events in the treatment group was higher than that in the control group, the difference was not statistically significant (P > 0.05). Conclusion: Butylphthalide combined with alteplase can significantly improve the degree of neurological deficit and prognosis in patients with acute cerebral infarction, with high safety.

Keywords:Butylphthalide, Alteplase, Acute Cerebral Infarction, Neurological Deficit, Prognosis

Copyright © 2023 by author(s) and Hans Publishers Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).

http://creativecommons.org/licenses/by/4.0/

1. 引言

脑梗死是危害我国国民健康的常见慢性病之一，是我国成人致死、致残的首要原因 [1] 。其具有高发病率、高致残率、高复发率、高病死率的特点给家庭和社会带来沉重的负担 [2] 。据全球疾病负担研究数据显示，我国脑梗死发病率呈逐年上升，且呈年轻化趋势 [2] 。对急性脑梗死患者，尽早开通血管，挽救缺血半暗带是早期治疗的主要策略 [3] 。《中国急性缺血性脑卒中诊治指南2018》明确指出，溶栓治疗是挽救缺血半暗带的主要方法 [4] 。目前标准剂量阿替普酶是我国静脉溶栓的首先溶栓药物 [4] [5] 。静脉溶栓最严重的并发症之一是症状性颅内出血，因此溶栓治疗后24小时内严禁使用抗血小板药物，这就使得急性脑梗死患者静脉溶栓后24小时内使用的药物非常有限，仍有一部分患者发生神经功能恶化 [6] 。丁苯酞是一种治疗急性脑梗死的新药，是从芹菜籽中提取的化合物，包含一系列光学异构体，其中包括l-3-正丁基苯酞(l-NBP)、d-3-正丁基苯酞(d-NBP)和dl-3-正丁基苯酞(dl-NBP)。l-NBP是芹菜油中的化学成分之一，而dl-NBP是合成的，是治疗神经疾病的重要神经保护药物，可自由穿过血脑屏障。此外，它被迅速吸收，半衰期较长，因此它具有持久的药理作用 [7] ，具有改善微循环，抑制氧化应激，保护线粒体，减少神经元凋亡等一系列病理机制 [8] - [13] 。然而，在急性脑梗死患者静脉溶栓后24小时内联合应用丁苯酞治疗的临床疗效尚不明确。本研究的目的是探讨丁苯酞联合阿替普酶对急性脑梗死患者静脉溶栓后神经功能缺损严重程度及预后的影响。

2. 资料和方法

2.1. 病例选择

2021年6月1日至2022年4月1日在临沂市人民医院神经内科住院治疗的首次急性脑梗死患者。纳入标准：1) 符合《中国急性缺血性脑卒中诊治指南2018》首发急性脑梗死诊断标准，经颅脑CT或MRI证实有急性脑梗死影像学改变；2) 年龄 > 18岁，发病时间4.5 h以内；3) 符合急性脑梗死阿替普酶静脉溶栓适应症；4) 患者或家属签署知情同意书。排除标准：1) 存在急性脑梗死阿替普酶静脉溶栓禁忌症；2) 进行机械取栓或血管内治疗的患者；3) 脑出血，蛛网膜下腔出血，严重全身感染，合并其他脏器严重疾病；4) 对芹菜过敏者；5) 患者或家属拒绝。

2.2. 方法

2.2.1. 资料收集

收集所有患者入院时一般临床资料(年龄、性别、高血压病史、糖尿病病史、房颤病史、吸烟史、饮酒史)，按照美国国立卫生院卒中量表(NIHSS)评定患者入院时、溶栓后24 h、溶栓后7天、出院时NIHSS评分，次日清晨抽取空腹血检测葡萄糖、甘油三酯、胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇等；所有患者溶栓24 h后均进行颅脑CT检查；记录患者溶栓过程中及溶栓后出现牙龈出血、鼻出血、消化道出血、脑出血及进展性卒中等并发症情况；90天随访按照改良Rankin量表(mRS)记录患者mRS评分。

2.2.2. 用药方法

根据入排标准将患者随机分为实验组和对照组。对照组给予注射用阿替普酶(爱通立) 0.9 mg/kg，最大剂量90 mg，静脉溶栓，10%在1 min内静脉推注，剩余90%1 h缓慢泵入。实验组在对照组基础上给予丁苯酞氯化钠注射液(恩必普) 100 ml静脉滴注，2次/d，治疗时间为7 d。两组患者溶栓后24 h复查颅脑CT，若无出血均给予抗血小板或抗凝治疗，其余均按照《中国急性缺血性脑卒中诊治指南2018》给予常规治疗。

2.3. 统计学分析

采用SPSS22.0统计软件对数据进行统计学分析。计量资料数据通过Kolmogorov-Smirnov检验证明是否为正态分布，服从正态分布用均数±标准差( x ¯ ± s )描述，组间比较采用独立样本t检验；计数资料用频率和百分比描述，组间比较采用χ2检验；P < 0.05 (双侧)为差异有统计学意义。

3. 结果

3.1. 两组患者一般临床资料比较

最终纳入首发急性脑梗死静脉溶栓患者200例，其中对照组98例，实验组102例。两组患者的一般临床资料进行比较差异无统计学意义(P > 0.05)，见表1。

Table 1. The comparison of general clinical data between the patients of two groups

表1. 两组患者一般临床资料比较

3.2. 两组患者生化指标比较

对两组患者生化指标进行比较发现血糖、血脂水平差异无统计学意义(P > 0.05)，见表2。

Table 2. Comparison of biochemical indexes between the two groups

表2. 两组患者生化指标比较

3.3. 两组患者入院时、溶栓后24 h、溶栓后7 d及出院时NIHSS评分比较

与对照组相比，实验组入院时NIHSS评分差异无统计学意义(P > 0.05)；与对照组相比，实验组溶栓后24 h NIHSS评分差异无统计学意义(P > 0.05)；与对照组相比，实验组静脉溶栓后7天及出院时NIHSS评分显著低于对照组，差异有统计学意义(P < 0.05)；见表3。

3.4. 随访90 d两组患者mRS评分比较

随访第90 d，记录患者mRS评分，与对照组相比，实验组mRS评分为0~2分的人数显著增加，差异有统计学意义(P < 0.05)，见表4。

3.5. 两组患者不良事件发生率比较

对照组牙龈出血2人，鼻出血2人，脑出血1人，进展性卒中3人；实验组牙龈出血4人，鼻出血2人，脑出血2人，消化道出血1人，进展性卒中3人。与对照组相比，实验组不良事件发生率差异无统计学意义(P > 0.05)，见表5。

Table 3. Comparison of NIHSS scores between the two groups at admission, 24 h after thrombolysis, 7 days after thrombolysis and on the day of discharge

表3. 两组患者入院时、溶栓24 h、溶栓后7天及出院当天NIHSS评分比较

Table 4. Comparison of 90-day mRS scores between the two groups

表4. 两组患者90天mRS评分比较

Table 5. Comparison of the incidence of adverse events between the two groups

表5. 两组患者不良事件发生率比较

4. 讨论

急性脑梗死是脑血管疾病中最常见的卒中类型，约占我国脑卒中的69.6%~70.8%。该病发病急、进展迅速，因此快速识别脑卒中，早期干预是减少卒中致死、致残的主要手段。急性脑梗死是原位血栓或栓子阻塞血管引起的脑组织缺血缺氧坏死。尽早恢复闭塞血管再通，恢复脑组织血流灌注，挽救缺血半暗带是降低脑梗死致死率、致残率的重要方法。《中国急性缺血性脑卒中诊治指南2018》明确静脉溶栓治疗是挽救缺血性脑组织的主要治疗方法 [4] ，但是只有46%的患者实现血管再通 [14] ，因此加快损伤组织处血管再生，减轻损伤组织处的炎症反应就显得尤为重要。

丁苯酞是从芹菜籽中提取出来的小分子物质，是治疗神经系统疾病的重要神经保护药物。可自由穿过血脑屏障 [7] 。丁苯酞的主要药理作用包括重建微循环、保护线粒体功能、抑制氧化应激、抑制炎症反应和抑制神经元凋亡 [15] - [20] 。此外，它还被发现具有抗血小板聚集、抗血栓形成、抗动脉粥样硬化、减轻脑水肿、改善脑灌注、减小梗死面积的作用 [21] [22] [23] [24] 。Chun-Sheng Yang等人的研究表明正丁基苯酞可直接靶向脑血管内皮细胞，抑制血管炎症的激活，保持血脑屏障的完整性及微血管的通畅，从而减轻神经血管炎症反应和缺血性脑损伤 [20] 。Pan-Ting Zhou等人的研究表明正丁基苯酞可以通过增加血管生成生长因子VEGF和Ang-1的表达，从而促进脑梗死周围区域的血管生成，进而减少MCAO大鼠的脑梗塞体积和神经功能缺损 [21] 。

丁苯酞还能抑制氧自由基的释放，提高缺血性脑损伤时抗氧化酶的活性 [19] 。这种作用最终将产生一系列效应，包括保护血管结构的完整性和恢复血管直径，改善局部微循环，增加脑缺血期间的血流量和毛细血管数量 [9] 。因此，丁苯酞在缺血性脑卒中的临床应用越来越广泛。本研究纳入的200例急性脑梗死静脉溶栓患者中，阿替普酶与丁苯酞联合治疗组治疗后7天及出院时神经功能缺损程度明显低于单用阿替普酶组，并且随访90天，阿替普酶联合丁苯酞治疗组预后良好人数明显多于单用阿替普酶组，两组不良事件发生率没有显著差异。

本研究结果提示，丁苯酞联合阿替普酶能显著改善急性脑梗死患者神经功能缺损程度及预后，且安全性较高。

文章引用

胡月圆,车峰远. 丁苯酞联合阿替普酶对急性脑梗死患者静脉溶栓后神经功能缺损严重程度临床疗效观察
Clinical Efficacy Observation of Butylphthalide Combined with Alteplase on the Severity of Neurological Deficit in Patients with Acute Cerebral Infarction after Intravenous Thrombolysis[J]. 临床医学进展, 2023, 13(03): 5052-5058. https://doi.org/10.12677/ACM.2023.133716

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    25. NOTES

    *通讯作者。

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