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银杏叶提取物联合低频重复经颅磁刺激治疗缺血性脑卒中的临床研究

The Clinical Efficacy and Possible Mechanism of Combination Treatment of Cerebral Ischemic Stroke with Ginkgo Biloba Extract and Low-Frequency Repetitive Transcranial Magnetic Stimulation

  • 摘要:
      目的  探讨银杏叶提取物联合低频重复经颅磁刺激(low frequency repetitive transcranial magnetic stimulation, LF-rTMS)治疗对缺血性脑卒中(cerebral ischemic stroke, CIS)患者氧化应激反应及脑神经递质的影响。
      方法  采用回顾性分析,选择2018年1月−2020年1月四川省人民医院收治的CIS患者93例为研究对象,按治疗方法不同分为常规组、LF-rTMS组、联合组,每组各31例。常规组给予常规药物治疗及康复疗法,LF-rTMS组在常规组的基础上给予LF-rTMS治疗(20~30 min/次,1次/d,5次/周),联合组在LF-rTMS组的基础上给予银杏叶提取物注射(静脉滴注,1次/d)。连续治疗4周。治疗4周末,比较3组临床疗效、氧化应激反应及脑氧代谢指标、脑神经递质频率等。
      结果  联合组有效率(96.77%)高于LF-rTMS组(80.65%)和常规组(54.84%)(P<0.05),LF-rTMS组有效率高于常规组(P<0.05)。联合组血清超氧化物歧化酶(superoxide dismutase, SOD)高于LF-rTMS组及常规组,丙二醛(malondialdehyde, MDA)和内皮素-1(endothelin-1, ET-1)低于LF-rTMS组及常规组(P<0.05),LF-rTMS组患者血清SOD高于常规组,MDA和ET-1低于常规组(P<0.05)。联合组动脉血氧(arterial oxygen content, CaO2)含量、动静脉血氧含量差(arterial-venous oxygen content difference, Ca-vO2)和脑氧摄取率(cerebral extraction rate of oxygen, CERO2)低于LF-rTMS组与常规组(P<0.05),LF-rTMS组上述3个指标低于常规组(P<0.05)。联合组γ-氨基丁酸(gamma-aminobutyric acid, GABA)、5-羟色胺(5-hydroxytryptamine, 5-HT)和多巴胺(dopamine, DA)脑电频率高于LF-rTMS组与常规组,乙酰胆碱(acetylcholine, Ach)脑电频率低于LF-rTMS组与常规组(P<0.05),LF-rTMS组GABA、5-HT和DA脑电频率高于常规组,Ach脑电频率低于常规组(P<0.05)。随访6个月,联合组复发率(3.23%)低于LF-rTMS组(19.35%)、常规组(25.81%)(P<0.05)。
      结论  银杏提取物联合LF-rTMS治疗有助于提高CIS患者临床疗效,可能与抑制氧化应激反应、改善脑氧代谢、调节脑神经递质等因素有关。

     

    Abstract:
      Objective  To study the effect of the combination treatment of ginkgo biloba extract and low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) on the oxidative stress and brain neurotransmitters of patients who had cerebral ischemic stroke (CIS).
      Methods  A retrospective analysis was conducted, and 93 CIS patients admitted to the Sichuan Academy of Medical Sciences/Sichuan Provincial People’s Hospital from January 2018 to January 2020 were included in the study. They were divided into three groups, the regular treatment group (31 cases), the LF-rTMS group (31 cases), and the combination treatment group (31 cases). Patients in the regular treatment group were given the conventional drug therapy and exercise regimen. The LF-rTMS group received LF-rTMS therapy (for 20-30 min each time, 1 time/d and 5 times/week) in addition to the treatment given to the regular treatment group. The combination treatment group was given ginkgo biloba extract (intravenous drips, once per day) in addition to the treatment given to the LF-rTMS group. The treatment was given continuously for 4 weeks and comparison was made at the end of the 4-week treatment regarding the clinical efficacy, oxidative stress response, cerebral oxygen metabolism, and brain neurotransmitter as shown by the three groups.
      Results  The treatment efficacy in the combination treatment group (96.77%) was higher than those of the LF-rTMS group (80.65%) and the regular treatment group (54.84%). The LF-rTMS group showed higher treatment efficacy than that of the regular group. The serum superoxide dismutase (SOD) of the combination treatment group was higher than that of the LF-rTMS group and that of the routine group, while the malondialdehyde (MDA) and endothelin-1 (ET-1) of the combination treatment group were lower than those of the LF-rTMS group and the regular treatment group (P<0.05). The serum SOD of the LF-rTMS group was higher than that of the regular treatment group, while the MDA and ET-1 of the group was lower than those of the regular treatment group (P<0.05). The arterial oxygen content (CaO2), arterio-venous oxygen content difference (Ca-vO2) and cerebral extraction rate of oxygen (CERO2) in the combination treatment group were lower than those of the LF-rTMS group and the regular treatment group (P<0.05). The levels of these three indicators of the LF-rTMS group were lower than those of the regular treatment group (P<0.05). EEG frequencies of gamma-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT) and dopamine (DA) of the combination treatment group were higher than those of the LF-rTMS group and the regular treatment group, while the acetylcholine (Ach) EEG frequency of the combination treatment group was lower than that of the LF-rTMS group and regular treatment group (P<0.05). The LF-rTMS group showed higher GABA, 5-HT and DA EEG frequencies than those of the regular treatment group, while the Ach EEG frequency of the group was lower than that of the regular treatment group (P<0.05). All the patients were followed up for 6 months, and recurrence rate was lower in the combination treatment group (3.23%) than that of the LF-rTMS group (19.35%) and the regular treatment group (25.81%) (P<0.05).
      Conclusion  The combination treatment of ginkgo biloba extract and LF-rTMS helped to improve the clinical outcome of CIS patients, which may be related to the inhibition of oxidative stress, improvement in cerebral oxygen metabolism, and regulation of brain neurotransmitter.

     

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