Study on Effect of Ginkgo Ketone on Inflammatory Response and Cognitive Function in Patients with Acute Ischemic Stroke

doi:10.3969/j.issn.1673-5765.2016.11.009

Abstract

Abstract:

Objective To investigate the effect of Ginkgo ketone ester dispersible tablets on the inflammatory reaction and cognitive function after ischemic stroke and its clinical significance. Methods This study was a prospective, multi-center, clinical randomized and controlled trial. Patients with acute ischemic stroke from Neurological Department in Nanjing Drum Tower Hospital and Yangzhou First People's Hospital during October 2012 to June 2014 were recruited and randomly divided into therapeutic group (Ginkgo ketone ester dispersible tablets (0.15 tid) combined with aspirin group (0.1 qd) and control group (aspirin group (0.1 qd), medication 180 d). Fresh blood was harvested before treatment and 13±1 days after treatment from enrolled patients. Serum inflammatory cytokines (IL-1β, IL-6, IL-15, IL-17A, IL-23 and TNF-α) were detected by Milliplex Map multiple detection techniques. National Institutes Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), Mini-Metal State Examination (MMSE) and Montreal Cognitive

Assessment (MOCA) were applied to evaluate neurological deficits and cognitive decline before treatment and (13±1) d, (30±7) d, (90±7) d, (180±7) d after treatment, and to compare scale scores changes in two groups before and after treatment. Results A total of 60 patients were enrolled into study. Among whom, 8 cases were excluded due to non-eligible blood specimen; 27 cases of study group and 25 cases of control group were taken into statistical analysis. Treatment of (13±1) d, the serum IL-1 beta IL-1β ([1.55±0.43] pg/ ml vs [2.05±0.74] pg/ml, P <0.001), IL-15 ([1.88±0.82] pg/ml vs [3.17±1.93] pg/ml, P <0.001), IL-6 ([5.57±4.96] pg/ml vs [8.81±8.00] pg/ml, P =0.042), IL-17A ([5.11±1.51] pg/ml vs [6.67±2.24] pg/ ml, P <0.001), IL-23 ([0.42±0.88] pg/ml vs [0.67±0.98] pg/ml, P <0.001), TNF-alpha ([15.12±6.97] pg/ml vs [18.31±6.61] pg/ml, P =0.009) levels in therapeutic group were decreased significantly than that before treatment; while in the control group, only IL-15 ([2.01±0.72] pg/ml vs [2.53±1.20] pg/ml, P =0.036) level was significantly decreased compared with that of before treatment. After treatment (30±7) d, (90±7) d, (180±7) d in the therapeutic group, MMSE and MOCA scores were improved more significantly than that before treatment compared with the control group (P =0.036, 0.012 and 0.048), though the two scores were of no significant differences in two groups. Conclusion The combination of Ginkgo ketone ester dispersible tablets and aspirin can more obviously reduce serum inflammatory cytokines and improve their cognitive function compared with using aspirin alone in ischemic stroke patient.

Key words: Ginkgo ketone ester; Aspirin; Ischemic stroke; Inflammatory cytokines

摘要：

目的研究银杏酮酯分散片对缺血性卒中后炎症反应及认知功能的影响及临床意义。方法本研究为前瞻性临床随机对照试验，选取2012年10月-2014年6月在南京鼓楼医院和扬州市第一人民医院神经内科住院的急性缺血性卒中患者，并随机分为试验组[银杏酮酯分散片（0.15 g，tid）联合阿司匹林治疗（0.1 g qd）]和对照组[阿司匹林（0.1 g qd）治疗]，用药180 d。比较两组血清炎症因子白细胞介素（interleukin，IL）-1β、IL-6、IL-15、IL-17A、IL-23、肿瘤坏死因子（tumor necrosis factor， TNF-α）水平。使用美国国立卫生研究院卒中量表（National Institutes of Health Stroke Scale，NIHSS）、改良Rankin量表、简易精神状态量表（Mini-Mental State Examination，MMSE）、蒙特利尔认知量表（Montreal Cognitive Assessment，MOCA）评分评估两组治疗前及治疗后（13±1）d、（30±7）d、（90±7）d、（180±7）d的神经功能缺损和卒中后认知功能的改变，比较两组治疗前后量表评分的变化情况。结果研究纳入60例患者，因血液标本不合格脱落8例，纳入统计分析的有试验组27例，对照组25 例。治疗（13±1）d时，试验组血清I L-1β[（1.55±0.43）pg/ml vs（2.05±0.74）pg/ml，P <0.001]，IL- 15（[ 1.88±0.82）pg/ml vs（3.17±1.93）pg/ml，P<0.001]，IL-6（[ 5.57±4.96）pg/ml vs（8.81±8.00） pg/ml，P=0.042]，IL-17A[（5.11±1.51）pg/ml vs（6.67±2.24）pg/ml，P<0.001]，IL-23（[ 0.42±0.88） pg/ml vs（0.67±0.98）pg/ml，P <0.001]，TNF-alpha[（15.12±6.97）pg/ml vs（18.31±6.61）pg/ml， P =0.009]水平较用药前有显著下降；而在对照组中仅IL-15[（2.01±0.72）pg/ml vs（2.53±1.20）pg/ ml，P =0.036]较用药前有显著下降。两组各随访点MMSE和MOCA评分虽无显著差异，但试验组用药后（30±7）d、（90±7）d、（180±7）d与用药前MMSE相比，比对照组改善更显著（P分别为0.036、0.012和 0.048）。结论银杏酮酯分散片联合阿司匹林比单用阿司匹林能更显著降低急性缺血性卒中患者血清炎症因子水平，改善其认知功能。

关键词: 银杏酮酯; 阿司匹林; 缺血性卒中; 炎症因子

CHENG Hong-Yu, ZHANG Xin-Jiang, LI Shan-Shan, et al.. Study on Effect of Ginkgo Ketone on Inflammatory Response and Cognitive Function in Patients with Acute Ischemic Stroke[J]. Chinese Journal of Stroke, 2016, 11(11): 947-953.

程弘禹，张新江，李姗姗，刘斌，邵渊，徐运，张梅娟. 银杏酮酯对缺血性卒中患者血浆促炎因子及认知功能的作用研究[J]. 中国卒中杂志, 2016, 11(11): 947-953.

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