Zhang Xiaofeng, Wu Qiang, Wang Zhihui, Li Haimei, Dai Jie
Department of Neurology, Cangzhou Central Hospital Cangzhou 061001, Hebei, China.
Department of Neurology, Cangzhou Central Hospital Hejian District Cangzhou 061001, Hebei, China.
Am J Transl Res. 2022 Apr 15;14(4):2637-2646. eCollection 2022.
To analyze the clinical efficacy and possible mechanism of butylphthalide in treatment of acute ischemic stroke.
In this retrospective study, 127 patients with ischemic stroke, hospitalized during Jan. 2019 to Jan. 2021, were enrolled and as assigned to observation group (n=65) and control group (n=62) according to treatment methods. The control group received routine treatment, and the observation group was treated with butylphthalide injection in addition to conventional cure. The treatments lasted for 2 weeks in both groups. Subsequently, the recovery of neurological deficits (NIHSS) and Barthel index (BI) of the two groups of patients, cerebrovascular vascular reserve function (CVR) values and pulsation index (PI) before and after treatment, and the levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and recombinant basic fibroblast growth factor (bFGF) were detected. The expression of Keap1-Nrf2/ARE signaling pathway related molecules was detected by ELISA.
The overall response rate (ORR) of observation group was remarkably superior to that of control group (). NIHSS score obviously decreased while BI remarkably increased in both groups after treatment (all ); and the observation group showed an significantly higher BI score but significantly lower NIHSS score compared with the control group (all ). The CVR of the two groups of patients after treatment was significantly higher than that before treatment (), while PI was significantly lower than before treatment (); The CVR of observation-group after treatment was substantially higher than that of control-group (), while PI was lower than control-group (). Serum Keap1 levels of the two groups of patients after treatment were significantly higher than that before treatment (), while serum levels of NQO1, Nrf2, and ARE were significantly lower than that before treatment (P<0.05). The serum level of Keap1 in the observation group was remarkably higher than that of the control group (), while the serum levels of NQO1, Nrf2 and ARE were evidently lower than those in the control group (). The two groups had insignificant difference in incidence of adverse reactions ().
The butylphthalide can effectively improve the clinical efficacy of acute ischemic stroke, and promote patients' neurological function and activities of daily living. The mechanism may be that butylphthalide improves the CVR of patients, enhances the establishment of collateral compensatory vessels, and changes the expression of the Keap1-Nrf2/ARE signaling pathway, thereby exerting the neuroprotective effect. Clinically, butylphthalide may have good safety in adjuvant therapy of acute ischemic stroke.
分析丁苯酞治疗急性缺血性脑卒中的临床疗效及可能机制。
本回顾性研究纳入2019年1月至2021年1月期间住院的127例缺血性脑卒中患者，根据治疗方法分为观察组（n = 65）和对照组（n = 62）。对照组接受常规治疗，观察组在常规治疗基础上加用丁苯酞注射液治疗。两组治疗均持续2周。随后，检测两组患者神经功能缺损评分（NIHSS）及Barthel指数（BI）恢复情况、治疗前后脑血管储备功能（CVR）值及搏动指数（PI），以及脑源性神经营养因子（BDNF）、血管内皮生长因子（VEGF）和重组碱性成纤维细胞生长因子（bFGF）水平。采用ELISA法检测Keap1-Nrf2/ARE信号通路相关分子的表达。
观察组总有效率（ORR）显著高于对照组（）。两组治疗后NIHSS评分均明显降低，BI均显著升高（均）；且观察组BI评分显著高于对照组，NIHSS评分显著低于对照组（均）。两组患者治疗后的CVR均显著高于治疗前（），而PI均显著低于治疗前（）；观察组治疗后的CVR显著高于对照组（），而PI低于对照组（）。两组患者治疗后的血清Keap1水平均显著高于治疗前（），而血清NQO1、Nrf2和ARE水平均显著低于治疗前（P < 0.05）。观察组血清Keap1水平显著高于对照组（），而血清NQO1、Nrf2和ARE水平明显低于对照组（）。两组不良反应发生率差异无统计学意义（）。
丁苯酞可有效提高急性缺血性脑卒中的临床疗效，促进患者神经功能及日常生活活动能力恢复。其机制可能是丁苯酞改善患者的CVR，增强侧支代偿血管的建立，并改变Keap1-Nrf2/ARE信号通路的表达，从而发挥神经保护作用。临床上，丁苯酞在急性缺血性脑卒中辅助治疗中可能具有良好的安全性。
