依达拉奉右莰醇联合阿加曲班治疗急性缺血性脑卒中的临床研究

张掂; 韩若东; 李冰; 过之一

doi:10.16766/j.cnki.issn.1674-4152.004085

依达拉奉右莰醇联合阿加曲班治疗急性缺血性脑卒中的临床研究

doi: 10.16766/j.cnki.issn.1674-4152.004085

张掂¹,
韩若东^2, ,,
李冰³,
过之一¹

1.
亳州市人民医院药学部, 安徽亳州 236800
2.
亳州市人民医院重症医学科
3.
亳州市人民医院神经内科

基金项目:

安徽省高校科学研究重点项目 2022AH050688

详细信息

通讯作者:
韩若东，E-mail: hanruodongb@126.com

中图分类号: R743.3
计量
- 文章访问数: 6
- HTML全文浏览量: 4
- PDF下载量: 0
- 被引次数: 0
出版历程
- 收稿日期: 2024-05-04

Clinical study of edaravone dexborneol combined with argatroban in the treatment of acute ischemic stroke

1.
Department of Pharmacy, Bozhou People's Hospital, Bozhou, Anhui 236800, China

摘要

摘要: 目的本研究旨在探讨依达拉奉右莰醇与阿加曲班联合应用在急性缺血性脑卒中(AIS)患者中的临床治疗效果及其对神经功能、炎症水平、自由基水平的影响。方法选取2022年1月—2023年12月亳州市人民医院收治的80例AIS患者，使用随机数字表法将患者分为对照组(40例)和治疗组(40例)。对照组给予阿加曲班治疗，治疗组给予阿加曲班联合依达拉奉右莰醇治疗。比较2组的临床疗效、相关量表评分、血清炎症因子、自由基水平及不良反应发生情况。结果治疗后，治疗组的总有效率优于对照组[95.0%(38/40) vs. 80.0%(32/40)，P＜0.05]。治疗2周后，治疗组NIHSS评分、改良Rankin评分低于对照组，Barthel指数评分高于对照组(P＜0.05)。治疗组超敏C反应蛋白、白介素-1β、白介素-6、肿瘤坏死因子-α水平低于对照组(P＜0.05)。治疗组丙二醛、活性氧水平低于对照组，超氧化物歧化酶水平高于对照组(P＜0.05)。2组不良反应发生率比较差异无统计学意义(P>0.05)。结论依达拉奉右莰醇联合阿加曲班可以显著提高AIS的临床疗效，有效促进神经功能恢复，提高患者日常生活质量，抑制炎症因子表达，降低血清自由基水平。
- 依达拉奉右莰醇 /
- 阿加曲班 /
- 急性缺血性脑卒中 /
- 神经功能 /
- 炎症因子 /
- 自由基
Abstract: Objective To explore the clinical efficacy, neurological function, inflammatory levels, and free radical levels of edaravone dexborneol combined with argatroban in patients with acute ischemic stroke (AIS). Methods A total of 80 patients with AIS admitted to Bozhou People ' s Hospital from January 2022 to December 2023 were selected and divided into the control group (40 cases) and treatment group (40 cases) based on the random number method. The control group was given argatroban and the treatment group was given argatroban combined with edaravone dexborneol. The clinical efficacy, related scale scores, serum inflammatory factors, free radicals and the occurrence of adverse reactions were compared between the two groups. Results After treatment, the total efficacy rate for the treated group was significantly better than the achieved by the control group [95.0% (38/40) vs. 80.0% (32/40), P < 0.05]. After 2 weeks of treatment, the NIHSS score and modified Rankin score in the treatment group were lower than those in the control group, while the Barthel index score was higher than that in the control group (P < 0.05). The levels of hypersensitive C-reactive protein, interleukin-1β, interleukin-6, and tumor necrosis factor-α in the treatment group were lower than those in the control group (P < 0.05). The levels of malondialdehyde and reactive oxygen species in the treatment group were lower than those in the control group, while the level of superoxide dismutase was higher than that in the control group (P < 0.05). The difference in the incidence of adverse reactions between the two groups was not statistically significant (P>0.05). Conclusion Edaravone dexborneol combined with argatroban significantly improves the clinical efficacy of AIS, effectively promotes the recovery of neurological function, improves the quality of daily life of patients, inhibits the expression of inflammatory factors, and reduces the level of serum free radicals.
- Edaravone dexborneol /
- Argatroban /
- Acute ischemic stroke /
- Neurological function /
- Inflammatory factors /
- Free radicals
利益冲突 无

HTML全文

表 1 2组AIS患者一般资料比较

Table 1. Comparison of general data between two groups of AIS patients

项目	对照组(n=40)	治疗组(n=40)	统计量	P值
性别(男性/女性，例)	25/15	22/18	0.503^a	0.478
年龄(x±s，岁)	62.30±6.82	64.31±7.15	1.287^b	0.202
病程(x±s，h)	24.75±5.62	26.09±7.84	0.990^b	0.324
梗死部位(例)			1.602^a	0.659
基底节区	16	14
丘脑	9	12
脑叶	8	10
脑干	7	4
合并疾病(例)
糖尿病	16	19	0.457^a	0.499
高血压	24	23	0.052^a	0.820
冠心病	20	17	0.453^a	0.501
高脂血症	7	9	0.313^a	0.576
注：^a为χ²值，^b为t值。

下载: 导出CSV

表 2 2组AIS患者总有效率比较[例(%)]

Table 2. Comparison of total effective rate between two groups of AIS patients [cases (%)]

组别	例数	基本痊愈	显效	有效	无效	总有效
对照组	40	7(17.5)	16(40.0)	9(22.5)	8(20.0)	32(80.0)
治疗组	40	9(22.5)	18(45.0)	11(27.5)	2(5.0)	38(95.0)
注：2组患者总有效率比较，χ²=4.114，P=0.043。

下载: 导出CSV

表 3 2组AIS患者治疗前后相关评分比较(x±s，分)

Table 3. Comparison of relevant scores between two groups of AIS patients (x±s, score)

组别	例数	NIHSS评分		改良Rankin量表评分		Barthel指数评分
组别	例数	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
对照组	40	16.32±3.18	10.74±2.12^b	3.65±1.17	2.24±0.66^b	45.62±10.58	63.26±14.36^b
治疗组	40	16.95±2.31	8.48±1.44^b	3.62±0.96	1.97±0.48^b	47.50±9.29	69.38±12.52^b
统计量		1.014^a	31.105^c	0.125^a	4.376^c	0.844^a	4.128^c
P值		0.314	＜0.001	0.901	0.040	0.401	0.046
注：^a为t值，^c为F值；与同组治疗前比较，^bP＜0.05。

下载: 导出CSV

表 4 2组AIS患者治疗前后炎症因子比较(x±s)

Table 4. Comparison of inflammatory factors between two groups of AIS patients (x±s)

组别	例数	超敏C反应蛋白(mg/L)		白介素-1β(ng/L)		白介素-6(ng/L)		肿瘤坏死因子-α(ng/L)
组别	例数	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
对照组	40	10.34±2.65	7.18±2.37^b	18.97±3.75	15.12±1.30^b	7.38±0.19	4.78±1.32^b	38.25±4.61	17.21±1.63^b
治疗组	40	9.78±0.81	4.87±1.46^b	18.06±2.74	12.40±1.72^b	7.03±1.45	3.64±1.09^b	39.14±3.79	14.18±1.12^b
统计量		1.278^a	27.541^c	1.239^a	63.649^c	1.514^a	17.741^c	0.943^a	93.896^c
P值		0.205	＜0.001	0.218	＜0.001	0.131	＜0.001	0.348	＜0.001
注：^a为t值，^c为F值；与同组治疗前比较，^bP＜0.05。

下载: 导出CSV

表 5 2组AIS患者治疗前后自由基指标比较(x±s)

Table 5. Comparison of free radical indexes between two groups of AIS patients (x±s)

组别	例数	丙二醛(μmol/L)		活性氧(μmol/L)		超氧化物歧化酶(μU/L)
组别	例数	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
对照组	40	4.82±0.90	2.91±0.24^b	594.68±84.41	486.35±78.53^b	62.08±7.62	84.01±10.54^b
治疗组	40	4.65±0.74	1.86±0.32^b	585.53±62.95	412.27±55.32^b	61.73±4.25	107.38±9.67^b
统计量		0.923^a	275.620^c	0.550^a	23.785^c	0.254^a	106.770^c
P值		0.359	＜0.001	0.584	＜0.001	0.800	＜0.001
注：^a为t值，^c为F值；与同组治疗前比较，^bP＜0.05。

下载: 导出CSV

参考文献(25)

[1]	GBD 2019 STROKE COLLABORATORS. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019[J]. Lancet Neurol, 2021, 20(10): 795-820. doi: 10.1016/S1474-4422(21)00252-0
[2]	中国医师协会神经内科医师分会脑血管病学组. 急性脑梗死缺血半暗带临床评估和治疗中国专家共识[J]. 中国神经精神疾病杂志, 2021, 47(6): 324-335. Stroke Group, Society of Neurology, Chinese Medical Doctor Association. Chinese expert consensus on clinical evaluation and treatment of ischemic penumbra in acute cerebral infarction[J]. Chinese Journal of Nervous and Mental Diseases, 2021, 47(6): 324-335.
[3]	POWERS W J, RABINSTEIN A A, ACKERSON T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association[J]. Stroke, 2019, 50(12): e344-e418.
[4]	王虹, 王柳清, 张万里, 等. 静脉溶栓时间与急性轻型脑梗死及短暂性脑缺血发作患者早期认知功能的关系[J]. 中华全科医学, 2023, 21(1): 45-49. doi: 10.16766/j.cnki.issn.1674-4152.002808 WANG H, WANG L Q, ZHANG W L, et al. Relationship between time of intravenous thrombolysis and early cognitive function in patients with acute mild ischemic stroke and transient ischemic attack[J]. Chinese Journal of General Practice, 2023, 21(1): 45-49. doi: 10.16766/j.cnki.issn.1674-4152.002808
[5]	胡寅钦, 程记伟, 孙梦, 等. 阿加曲班治疗急性缺血性卒中疗效及安全性的系统评价及Meta分析[J]. 重庆医科大学学报, 2022, 47(7): 811-820. HU Y Q, CHENG J W, SUN M, et al. The efficacy and safety of argatroban in the treatment of acute ischemic stroke: a systematic review and meta-analysis[J]. Journal of Chongqing Medical University, 2022, 47(7): 811-820.
[6]	XU J, WANG A X, MENG X, et al. Edaravone Dexborneol versus edaravone alone for the treatment of acute ischemic stroke: a phase Ⅲ, randomized, double-blind, comparative trial[J]. Stroke, 2021, 52(3): 772-780. doi: 10.1161/STROKEAHA.120.031197
[7]	中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组. 中国急性缺血性卒中诊治指南2023[J]. 中华神经科杂志, 2024, 57(6): 523-559. Chinese society of neurology, Chinese stroke society. Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2023[J]. Chinese Journal of Neurology, 2024, 57(6): 523-559.
[8]	吴正欢, 史俊, 周梦奇, 等. 依达拉奉右莰醇注射用浓溶液联合己酮可可碱治疗急性脑梗死的临床研究[J]. 现代药物与临床, 2023, 38(3): 591-595. WU Z H, SHI J, ZHOU M Q, et al. Clinical study of Edaravone and Dexborneol Concentrated Solution for injection combined with pentoxifylline in treatment of acute cerebral infarction[J]. Drugs and Clinic, 2023, 38(3): 591-595.
[9]	李和侠, 刘惠娟, 尹伟, 等. 阿加曲班治疗急性期脑梗死52例临床疗效分析[J]. 中华全科医学, 2019, 17(7): 1112-1114, 1170. doi: 10.16766/j.cnki.issn.1674-4152.000876 LI H X, LIU H J, YIN W, et al. Clinical analysis of therapeutic effect of argatroban for acute cerebral infarction: a report of 52 cases[J]. Chinese Journal of General Practice, 2019, 17(7): 1112-1114, 1170. doi: 10.16766/j.cnki.issn.1674-4152.000876
[10]	COMER A R, TEMPLETON E, GLIDDEN M, et al. National Institutes of Health sroke scale (NIHSS) scoring inconsistencies between neurologists and emergency room nurses[J]. Front Neurol, 2023, 13: 1093392. DOI: 10.3389/fneur.2022.1093392.
[11]	SAVER J L, CHAISINANUNKUL N, CAMPBELL B C V, et al. Standardized nomenclature for modified rankin scale global disability outcomes: consensus recommendations from stroke therapy academic industry roundtable XI[J]. Stroke, 2021, 52(9): 3054-3062. doi: 10.1161/STROKEAHA.121.034480
[12]	FU M, FAN Y N, YAN S M, et al. Barthel index, SPAN-100, and NIHSS studies on the predictive value of prognosis in patients with thrombolysis[J]. Neurologist, 2024, 29(3): 158-162. doi: 10.1097/NRL.0000000000000554
[13]	吴健隆, 张潇, 江文. 缺血性脑卒中神经保护药物的临床研究进展[J]. 中国实用神经疾病杂志, 2023, 26(10): 1311-1316. WU J L, ZHANG X, JIANG W. Clinical research progress of neuroprotective drugs for ischemic stroke[J]. Chinese Journal of Practical Nervous Diseases, 2023, 26(10): 1311-1316.
[14]	CHENG Y R, LIU C N, LI S S, et al. Efficacy and safety of Argatroban in patients with acute ischemic stroke: a systematic review and meta-analysis[J]. Front Neurol, 2024, 15: 1364895. DOI: 10.3389/fneur.2024.1364895.
[15]	ZHANG X T, ZHONG W S, XUE R, et al. Argatroban in patients with acute ischemic stroke with early neurological deterioration: a randomized clinical trial[J]. JAMA Neurol, 2024, 81(2): 118-125. doi: 10.1001/jamaneurol.2023.5093
[16]	齐英斌, 许卓, 周艳, 等. 依达拉奉右莰醇对老年缺血性脑卒中患者脑细胞的保护作用[J]. 中国老年学杂志, 2024, 44(8): 2035-2037. QI Y B, XU Z, ZHOU Y, et al. Protective effect of edaravone and dexborneol on brain cells in elderly patients with ischemic stroke[J]. Chinese Journal of Gerontology, 2024, 44(8): 2035-2037.
[17]	郭慧, 秦鼎, 焦鸿云, 等. 依达拉奉右莰醇注射用浓溶液联合阿加曲班治疗急性脑梗死的临床研究[J]. 现代药物与临床, 2023, 38(4): 834-839. GUO H, QIN D, JIAO H Y, et al. Clinical study of edaravone and dexborneol concentrated solution for injection combined with agatroban in treatment of acute cerebral infarction[J]. Drugs and Clinic, 2023, 38(4): 834-839.
[18]	ENDRES M, MORO M A, NOLTE C H, et al. Immune pathways in etiology, acute phase, and chronic sequelae of ischemic stroke[J]. Circ Res, 2022, 130(8): 1167-1186. doi: 10.1161/CIRCRESAHA.121.319994
[19]	YALCINKAYA M, FOTAKIS P, LIU W L, et al. Cholesterol accumulation in macrophages drives NETosis in atherosclerotic plaques via IL-1β secretion[J]. Cardiovasc Res, 2023, 119(4): 969-981. doi: 10.1093/cvr/cvac189
[20]	江娜, 许元, 冯林玉, 等. 中性粒细胞在缺血性脑卒中的作用研究进展[J]. 神经损伤与功能重建, 2023, 18(11): 651-655, 666. JIANG N, XU Y, FENG L Y, et al. Role of neutrophils in ischemic stroke[J]. Neural Injury and Functional Reconstruction, 2023, 18(11): 651-655, 666.
[21]	WANG D X, WANG Y T, SHI J F, et al. Edaravone Dexborneol alleviates ischemic injury and neuroinflammation by modulating microglial and astrocyte polarization while inhibiting leukocyte infiltration[J]. Int Immunopharmacol, 2024, 130: 111700. DOI: 10.1016/j.intimp.2024.111700.
[22]	ZIETZ A, GOREY S, KELLY P J, et al. Targeting inflammation to reduce recurrent stroke[J]. Int J Stroke, 2024, 19(4): 379-387. doi: 10.1177/17474930231207777
[23]	BRIONES-VALDIVIESO C, BRIONES F, ORELLANA-URZŪA S, et al. Novel multi-antioxidant approach for ischemic stroke therapy targeting the role of oxidative stress[J]. Biomedicines, 2024, 12(3): 501. DOI: 10.3390/biomedicines12030501.
[24]	孙春梅, 唐玲, 庹玉平. 依达拉奉介导氧自由基清除促进脑卒中大鼠血脑屏障修复[J]. 徐州医科大学学报, 2022, 42(8): 583-587. SUN C M, TANG L, TUO Y P. Edaravone-mediated oxygen radical scavenging promotes blood-brain barrier repair in rats with stroke[J]. Journal of Xuzhou Medical University, 2022, 42(8): 583-587.
[25]	LI Y, REN M H, WANG J J, et al. Progress in borneol intervention for ischemic stroke: a systematic review[J]. Front Pharmacol, 2021, 12: 606682. DOI: 10.3389/fphar.2021.606682.