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CCMP94-RD-031 川芎之活性生物鹼tetramethylpyrazine併用aspirin對預防缺血性腦梗塞之研究

  • 資料來源:中醫藥司
  • 建檔日期:94-01-02
  • 更新時間:109-02-18

川芎之活性生物鹼tetramethylpyrazine併用aspirin對預防缺血性腦梗塞之研究

許準榕
台北醫學大學
目前,抗血小板藥物已被建議使用在預防臨床上各類血管的病變,例如心肌梗塞、中風和心血管疾病。 在臨床上,目前已有數類抗血小板藥物應用在預防繼發性缺血性中風的產生,包含了aspirin、ADP receptor anagonist (ticlopidine和clopidogrel)以及glycoprotein IIb/IIIa antagonist,aspirin的作用機轉為不可逆的抑制cyclooxygenase而減少了thromboxane A2的生合成及抑制血小板的凝集,在這幾類藥物中,由於aspirin在預防繼發性缺血性中風的臨床試驗多、證據多、經濟效應好且具有不錯的療效,有23%減少中風發生的危險率及18%減少中風、心肌梗塞及血管死亡發生的危險率,所以aspirin亦是目前用來預防繼發性缺血性中風的首選藥物,同時為了要提高預防繼發性缺血性中風的效果,已有臨床試驗(ESPS II study)併用兩種不同作用機轉的抗血小板藥物長效型的dipyridamole及aspirin來做測試,發現的確能提高至37%減少中風發生的危險率,且在副作用的產生與單獨使用aspirin並無意義增加,同時亦有另一組臨床試驗(MATCH study)正在評估clopidogrel併用aspirin來預防中風的效果。 由於我們先前的計畫利用川芎之活性生物鹼tetramethylpyrazine (TMPZ)來預防中風的動物模式中,我們發現TMPZ (20 mg/kg)能有義意的減少腦梗塞面積約60%的相對減少率(P<0.01),其可能的作用機轉包含了1. 抗血小板活性的作用:TMPZ能夠促進cGMP的含量增加以及抑制phospholipase C的活性,2. 抗氧化的作用。 所以,本計畫的目的主要是併用TMPZ和aspirin來探討此兩種不同作用機轉的抗血小板藥物是否能更有效預防中風的形成,其研究方法為利用大腦中動脈血管阻塞/再灌流模式動物實驗模式來造成缺血性腦中風,進而再評估此兩種藥物併用後之作用效果,其評估方法包括:腦梗塞區域之測定、行為測試、脂質過氧化的測量、神經缺陷分級和抓力測試。
關鍵字:抗血小板;缺血性中風;aspirin;tetramethylpyrazine

Study the effect of tetramethylpyrazine combined with aspirin on ischemic cerebral infarction

Joen-Rong Sheu
Graduate Institute of Medical Sciences, Taipei Medical University
Recently, a vast amount of randomized data supports the use of antiplatelet drugs to prevent serious vascular events (stroke, MI, and vascular death) in a wide range of patients at high vascular risk (eg, stroke survivors, MI survivors, claudicants). Several antiplatelet agents with different mechanisms of action are currently available for secondary prevention of ischemic stroke. They include aspirin, ADP receptor antagonist (ticlopidine and clopidogrel) and glycoprotein IIb/IIIa antagonist. Aspirins mechanism of action is irreversible inhibition of cyclooxygenase, resulting in reduction of thromboxane A2 biosynthesis and attenuation of platelet aggregation. Of all antiplatelet agents, aspirin has more clinical trials, evidence and modest efficacy, and is inexpensive in secondary prevention of ischemic stroke. Aspirin leads to a modest reduction both in the risk of stroke (23%) and the combined end point of stroke, myocardial infection (MI), or vascular death (18%). Therefore, all data suggested that aspirin should be first-line antiplatelet therapy in the secondary prevention of stroke.
關鍵字:antiplatelet;ischemic stroke;aspirin;tetramethylpyrazine