Objective To investigate the effect of Dl-3-n-butylphthalide on acute cerebral infarction. Methods In Department of Neurology in the Fifth Hospital of Wuhan from March 2013 to June 2014, 100 cases of patients with first onset of acute cerebral infarction were recruited. The participants were divided into 2 groups (control group and treatment group) randomly, with 50 participants in each group. Besides general treatment, the patients of treatment group received intravenous injection of Dl-3-n-butylphthalide in acute phase and orally took soft capsule of Dl-3-n-butylphthalide in recovery phase. All the patients were followed up for 24 weeks. Neurological function and general cognition were assessed separately by national institute of health stroke scale (NIHSS), and mini mental state examination (MMSE) was applied to assess overall cognitive function. Results NHISS score was gradually decreased and MMSE score was increased in both groups. As compared with the control group, NIHSS score and MMSE score were changed significantly in the treatment group. From first onset to 24 weeks after treatment, NHISS score was decreased by 30% in the control group and 44% in the treatment group; MMSE score was increased by 17% in the control group and 32% in the treatment group. Conclusion Sequential therapy with Dl-3-n-butylphthalide improves neurological function and general cognition faster and more significant for patients with acute cerebral infarction.
收集武汉市第五医院神经内科2013年3月-2014年7月的急性脑梗死患者共100例,其中男性、女性各50名,年龄45~75岁。入组标准:均符合缺血性卒中的诊断标准,经头颅CT和(或)MRI检查确诊为脑梗死,发病24 h内入院,美国国立卫生研究院卒中量表评分(national institute of health stroke scale,NIHSS)为17分以下,均未行溶栓治疗。排除标准:①并发血液系统疾病、自身免疫疾病如系统性红斑狼疮和干燥综合征、甲状腺功能亢进或甲状腺功能减退、结核病、肿瘤、严重肝肾疾病等各系统严重病变;②发病前2周内曾有严重感染;③过敏体质患者。退出标准:①出现严重不良反应,如严重皮疹、肝肾功能衰竭、过敏性休克等;②出现心脑血管病事件,如心肌梗死、脑出血、脑梗死再发等;③不可预测的突发意外死亡。将100例脑梗死入院患者采用随机数字表法分为对照组和治疗组各50例。所有研究对象用药均征得患者本人和家属同意,获得我院伦理委员会一致通过,所有患者签署知情同意书。两组患者性别、年龄、血压、血糖、体重指数、血脂、吸烟史、饮酒史、入院时NIHSS评分、白细胞计数等均差异无统计学意义(均P>0.05),具有可比性。见表1。
表1
Tab.1
表1
表1
两组患者一般资料比较
Tab.1
Comparison of baseline data between two groups of patients n=50
组别
年龄/ 岁
性别
既往史
女 例
男
糖尿病
高血脂
高血压
例
%
例
%
例
%
对照组
64.72±2.7
25
25
15
30.0
7
14.0
42
84.0
治疗组
63.35±4.7
25
25
17
34.0
5
10.0
39
78.0
表1
两组患者一般资料比较
Tab.1
Comparison of baseline data between two groups of patients n=50
应用SPSS18.0(PASW Statistics version 18.0)版统计软件,计量资料以均数±标准差(
±s)表示,3组间年龄等计量资料采用单因素方差分析,性别组成及既往史组成采取卡方检验。分别对NHISS、MMSE采取治疗(对照组/治疗组)×随访时间(基线期/2周/4周/8周/12周/16周)双因素方差分析。以P<0.05为差异有统计学意义。
JIAJ,WEIC,LIANGJ,et al.The effects of Dl-3-n-butylphthalide in patients with vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease:a multicentre,randomized,double-blind,placebo-controlled trial[J].Alzheimers Dement,2016,12(2): 89-99.
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[2]
SUNB,FENGM,TIANX,et al.Dl-3-n-butylphthalide protects rat bone marrow stem cells against hydrogen peroxide-induced cell death through antioxidation and activation of PI3K-Akt pathway[J].Neurosci Lett,2012,516(2): 247-252.
Bone marrow stem cells (BMSCs) have been one of the most important cell sources for cell replacement therapy (CRT) in cerebral infarction. However, long-lasting oxidative stress during stroke, which plays an important role in neuron damage, deteriorates the microenvironment for cell survival, differentiation and removal. Thus the outcome of CRT in ischemic diseases was poor. DL-3-n-Butylphthalide (NBP) has protective effects on ischemic brain tissue through multiple mechanisms and has been used for stroke treatment in China for several years. In this study, hydrogen peroxide (H2O2) was used to induce oxidative stress injury to rat bone marrow stem cells (rBMSCs), imitating the microenvironment surrounding transplanted cells in the ischemic brain in vitro. The protective effects of NBP on rBMSCs against apoptosis induced by oxidative stress were investigated. Our results indicated that NBP could protect rBMSCs against apoptosis due to antioxidative properties and modulation of PI3K/Akt pathway. NBP could be used in combination with BMSCs for the treatment of cerebral infarction by improving the oxidative stress microenvironments and cell survival, however, further studies remain warranted. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
ZHANGL,LUL,CHAN WM,et al.Effects of Dl-3-n-butylphthalide on vascular dementia and angiogenesis[J].Neurochem Res,2012,37(5): 911-919.
3-n-Butylphthalide (NBP) is a compound extracted from Chinese celery and is used as an anti-hypertensive herbal medicine for treating stroke patients. The aim of this study is to demonstrate the effects and mechanisms of this compound through in vitro and in vivo experiments. Culture experiments were performed by adding hydrogen peroxide (H2O2) to SH-SY5Y cells. From the MTT assay result, enhanced cell survival was observed with DL-NBP treatment, regardless of whether they are added before, simultaneously with or after the addition of H2O2. For the in vivo experiment, Spontaneously Hypertensive rats and Wistar Kyoto control rats with chronic cerebral ischemia, which were induced by bilateral transection of the common carotid arteries, were given DL-NBP. Their performances in the place navigation test and spatial probe test in the Morris Water Maze have significantly improved compared with the DL-NBP untreated animals, indicating an improvement in spatial learning and memory in the ischemic-animals. In addition, in the chick embryonic chorioallantoic membrane assay, angiogenesis was more vigorous under the effects of DL-NBP, together with increased expression of growth factors, VEGF, VEGF-receptor and bFGF. All these suggested that one of the mechanisms of DL-NBP might be ameliorating vascular dementia and promoting angiogenesis.
ZHANGL,YU WH,WANG YX,et al.Dl-3-n-butylphthalide,an anti-oxidant agent,prevents neurological deficits and cerebral injury following stroke per functional analysis,magnetic resonance imaging and histological assessment[J].Curr Neurovasc Res,2012,9(3): 167-175.
DL-3-n-Butylphthalide (NBP) is a synthetic compound based on L-3-n-Butylphthalide which was isolated from seeds of Apium graveolens. The present study aims at evaluating the outcome of NBP given prior to and after the onset of ischemic stroke in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Stroke was induced by the middle cerebral artery occlusion (MCAO) in SHR and WKY. For pre-treatment, NBP was administered to SHR and WKY daily for two months prior to MCAO. For post-treatment, NBP was given daily for seven consecutive days after MCAO. Seven days post-surgery, rats were tested for the presence of neurological deficits. Magnetic resonance imaging (MRI) and 2,3,5-triphenyltetrazolium chloride (TTC) staining were employed to calculate the infarct volume. The cerebral cortex and corpus striatum in the ischemic penumbra area were examined microscopically for pathological changes. In SHR, NBP pre- and post-treatment significantly lowered neurological deficit scores, reduced infarct volume, and minimized pathological changes in the penumbra area when compared to oil-vehicle treated controls. In WKY, these beneficial effects were observed only in the post-treatment group. The beneficial effects of NBP post-treatment were greater in WKY than in SHR. Results indicated that NBP could exert both preventive and therapeutic effects on ischemic stroke in SHR, but only exerted therapeutic effect in WKY.
ADAMS HJ,DAVIS PH,LEIRA EC,et al.Baseline NIH stroke scale score strongly predicts outcome after stroke: a report of the trial of org 10172 in acute stroke treatment (TOAST)[J].Neurology,1999,53(1): 126-131.
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[13]
LIJ,LIY,OGLEM,et al.Dl-3-n-butylphthalide prevents neuronal cell death after focal cerebral ischemia in mice via the JNK pathway[J].Brain Res,2010,1359(4): 216-226.
dl -3- n -Butylphthalide (NBP) has shown cytoprotective effects in animal models of stroke and has passed clinical trials as a therapeutic drug for stroke in China. Hence, as a potential clinical treatment for stroke, understanding the mechanism(s) of action of NBP is essential. This investigation aimed to delineate the cellular and molecular mechanism of NBP protection in neuronal cultures and in the ischemic brain. NBP (1002μM) attenuated serum deprivation-induced neuronal apoptosis and the production of reactive oxygen species (ROS) in cortical neuronal cultures. Adult male 129S2/sv mice were subjected to permanent occlusion of the middle cerebral artery (MCA). NBP (10002mg/kg, i.p.) administrated 202hrs before or 102hr after ischemia reduced ischemia-induced infarct formation, attenuated caspase-3 and caspase-9 activation in the ischemic brain. TUNEL-positive cells and mitochondrial release of cytochrome c and apoptosis-inducing factor (AIF) in the penumbra region were reduced by NBP. The proapoptotic signaling mediated by phospho-JNK and p38 expression was downregulated by NBP treatment in vitro and in vivo. It is suggested that NBP protects against ischemic damage via multiple mechanisms including mitochondria associated caspase-dependent and -independent apoptotic pathways. Previous and current studies and recent clinical trials encourage exploration of NBP as a neuroprotective drug for the treatment of ischemic stroke.
YEJ,ZHAIL,ZHANGS,et al.Dl-3-n-butylphthalide inhibits platelet activation via inhibition of cPLA2-mediated TXA2 synthesis and phosphodiesterase[J].Platelets,2015,26(8): 736-744.
Abstract Abstract Aberrant platelet activation plays a critical role in the pathogenesis of heart attack and stroke. dl-3-n-butylphthalide (NBP) has been approved in China to treat stroke with multiple mechanisms. The anti-stroke effects of NBP may be related to its antiplatelet effects reported in rats in addition to its antioxidative, antiapoptotic, and angiogenic effects. However, the effects and the underlying mechanisms of NBP on human platelets are not yet clear. In this study, we found that NBP concentration-dependently inhibited human platelet aggregation and ATP release induced by ADP, thrombin, U46619, arachidonic acid, or collagen. NBP also inhibited PAC-1 binding induced by ADP or thrombin and platelet spreading on immobilized fibrinogen. NBP reduced TXA2 synthesis induced by thrombin or collagen via inhibiting cPLA2 phosphorylation, concomitantly with a marked decrease in intracellular calcium mobilization. Moreover, NBP also inhibited human platelet phosphodiesterase (PDE) and elevated 3,5-cyclic adenosine monophosphate level in platelets. In conclusion, NBP significantly inhibits human platelet activation via inhibition of cPLA2-mediated TXA2 synthesis and PDE, and may be effective as an antiplatelet drug to treat other arterial thrombotic diseases.
The effects of 3-butylphthalide in patients with vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease:a multicentre,randomized,double-blind,placebo-controlled trial
3-butylphthalide protects rat bone marrow stem cells against hydrogen peroxide-induced cell death through antioxidation and activation of PI3K-Akt pathway
3-butylphthalide,an anti-oxidant agent,prevents neurological deficits and cerebral injury following stroke per functional analysis,magnetic resonance imaging and histological assessment
, 李鸣, 肖家平, 李强
