中文大、北大顶级期刊Lancet发布研究进展

　　

生物通报道，来自香港中文大学医疗系，新加坡国立大学药理系，上海华山医院，北京大学附属第一医院的科学家近期在Lancet发布最新研究进展文章Clopidogrel plus aspirin versus aspirin alone for reducing embolisation in patients with acute symptomatic cerebral or carotid artery stenosis (CLAIR study): a randomised, open-label, blinded-endpoint trial。

 

大部分的脑中卒都源自脑部血管栓塞。对于某些血液中有微栓子或是小的血凝块的人而言，他们脑中卒发生几率将升高很多。

 

来自香港中文大学的Lawrence Ka Sing Wong与研究团队的人员合作进行的随机临床试验发现，调查分析抗血凝药作为中卒二次预防的临床效果。

 

研究结果显示，联合用药，阿司匹林配合clopidogrel使用预防脑内微小栓塞的效果比单独使用阿司匹林的效果更加。

 

研究小组选用100名近期有中卒病史的患者进行追踪调查，其中47名患者接受双重用药试验，另外的53名患者接受单一用药试验，这是个为期7天的临床试验。在试验过程中，第二天和第七天，所有患者接受颅部多普勒扫描，观察脑部的微小栓塞信号。

 

在第二天，12名接受双重用药的病人和27名接受单一用药的病人经多普勒扫描发现有微小栓塞信号。在药物副作用方面，两组病人所表现的结果是相似的，只有2个接受双重用药的患者有轻微的出血现象。

 

这些研究结果表明，双重用药是一种更为有效减轻栓塞，预防二次中风的有效办法。研究小组下一步的研究计划是，分析计算双重用药方式降低中风几率的具体百分数。

 

近期Cell关于中卒研究

路易斯安那州大学医学院神经科学系，福罗里达州中心大学生物医学中心Wrigh State大学医学院的科学家最近在脑卒中治疗研究方面取得新的进展，相关成果文章DAPK1 Interaction with NMDA Receptor NR2B Subunits Mediates Brain Damage in Stroke公布在Cell杂志上，并且被列为当期的亮点文章。

 

文章通讯作者是来自，路易斯安那州大学医学院神经科学系的鲁友明教授，早年毕业于中国药科大学，主要从事脑卒中和阿尔茨海默病的信号分子通路课题研究。

 

在神经突触外，谷氨酸的主要亚型受体是N-甲基-D-天（门）冬氨酸（NMDA）受体，NMDA与多种细胞内引发不可逆的神经元死亡的分解代谢活动有关。

 

在本研究中，鲁友明教授组的科学家研究分析了小鼠大脑皮层中因脑缺血而诱发的神经元死亡蛋白激酶1（death-associated protein kinase1）与NMDA受体NR2B蛋白复合物的作用过程。

 

死亡相关蛋白激酶DAPK1可直接与NMDA受体NR2B蛋白氨基端尾巴结合。接下来激活DAPK1磷酸化的NR2B亚单位ser-1303，依次激活NR1/NR2B受体通道的传导效率。如果用遗传学技术将DAPK1基因缺失掉，将导致NR1/NR2B通路失活，导致大脑神经元细胞失去局部缺氧环境的保护伞。

 

DAPK1在生理和功能上与NMDA受体NR2B亚单位作用，它的功效的发挥与脑卒中有着密切的关联，因此，可能成为治疗脑卒中的一个适当途径。　脑卒中（Stroke）是脑中风学名，是一种突然起病的脑血液循环障碍性疾病。

 

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Wong, K. S. L. et al. Clopidogrel plus aspirin versus aspirin alone for reducing embolisation in patients with acute symptomatic cerebral or carotid artery stenosis (CLAIR study): a randomised, open-label, blinded-endpoint trial. Lancet doi:10.1016/S1474-4422(10)70060-0 (2010). | Article

Abstract

BACKGROUND: Few randomised clinical trials have investigated the use of antithrombotic drugs for early secondary prevention of stroke or transient ischaemic attack in patients with intracranial atherosclerotic stenosis. Microembolic signals, detected by transcranial doppler, are a surrogate marker of future stroke risk and have been used to show treatment efficacy in patients with extracranial carotid stenosis. We aimed to investigate whether treatment with clopidogrel plus aspirin reduced the number of microembolic signals detected with transcranial doppler ultrasound compared with aspirin alone in patients with recent stroke. METHODS: The clopidogrel plus aspirin for infarction reduction in acute stroke or transient ischaemic attack patients with large artery stenosis and microembolic signals (CLAIR) trial was a randomised, open-label, blinded-endpoint trial. Between Oct 28, 2003, and Nov 19, 2008, patients with acute ischaemic stroke or transient ischaemic attack who had symptomatic large artery stenosis in the cerebral or carotid arteries and in whom microembolic signals were present on transcranial doppler were randomly assigned within 7 days of symptom onset to receive clopidogrel (300 mg for the first day, then 75 mg daily) plus aspirin (75-160 mg daily) or aspirin alone (75-160 mg daily) for 7 days. Patients were randomly assigned in blocks of four or six by use of a randomisation website. Monitoring of microembolic signals on transcranial doppler was done on days 2 and 7. The primary endpoint was the proportion of patients who had microembolic signals on day 2. Analysis was by modified intention to treat. All analyses were done by an investigator masked to both patient identity and the day the recording was taken. This trial is registered with the Centre for Clinical Trials, Chinese University of Hong Kong, number CUHK_CCT00164. FINDINGS: 100 patients were randomly assigned to clopidogrel plus aspirin (n=47) or aspirin monotherapy (n=53). 93 of 100 patients had symptomatic intracranial stenosis in either the intracranial internal carotid artery or the middle cerebral artery: 45 of 46 in the dual therapy group and 48 of 52 in the monotherapy group. At day 2, 14 of 45 patients in the dual therapy group and 27 of 50 patients in the monotherapy group for whom data were available had at least one microembolic signal on transcranial doppler (relative risk reduction 42.4%, 95% CI 4.6-65.2; p=0.025). Adverse events were similar in the two groups. No patients had intracranial or severe systemic haemorrhage, but two patients in the dual therapy group had minor haemorrhages. INTERPRETATION: Combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing microembolic signals in patients with predominantly intracranial symptomatic stenosis. Clinical trials are now warranted to investigate whether this combination treatment also results in a reduction in stroke incidence. FUNDING: Research Grant Council Earmarked Grant and Asian Stroke Research Grant, Chinese University of Hong Kong.