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題名 | 葛根之活性成分Puerarin併用Clopidogrel對預防缺血性腦梗塞之研究=Study the Effect of Puerarin Combined with Clopidogrel on Ischemic Cerebral Infarction |
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作者姓名(中文) | 許準榕; | 書刊名 | 中醫藥年報 |
卷期 | 25:1 2007.10[民96.10] |
頁次 | 頁525-551 |
專輯 | 中醫藥療效評估之研究 |
分類號 | 414.332 |
關鍵詞 | 抗血小板藥物; 缺血性中風; Puerarin; Clopidogrel; Antiplatelet drugs; Ischaemic stroke; |
語文 | 中文(Chinese) |
中文摘要 | 抗血小板藥物已被建議使用在預防各類血管的病變,例如心肌梗塞、中風和心血管疾病。臨床上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、ticlopidine和clopidogrel這兩個ADP antagonist以及glycoprotein IIb/IIIa antagonist。在這幾類藥物中,clopidogrel會經由抑制血小板上ADP受體的結合來抑制血小板凝集進而預防血管病變,由於血小板除了會經由ADP受體的活化而凝集外,其他刺激劑所造成的血小板凝集反應亦會經由釋出ADP,來放大血小板凝集反應,造成血栓的形成,故在臨床應用上,clopidogrel與常用的抗血栓藥物asipirin相較,更能有效的降低一些心血管疾病如心肌梗塞、缺血性中風發生的機率。 近來的研究指出葛根的活性成分puerarin(100mg/kg)在大鼠的缺血性中風動物模式中,能有效的減少缺血性中風所產生的腦損傷區域,並有保護腦細胞的功能,而其藥理機轉可能是經由抑制腦細胞的細胞凋亡來保護腦細胞進而改善缺血性腦梗塞所造成的傷害。 本計畫的目的主要是併用puerarin和clopidogrel來探討此兩種不同作用機轉的藥物是否能更有效預防中風的形成,抗血小板藥物在預防中風的臨床應用上,能否經由併用中藥而更增加其效果,並深入的探討其可能的分子機轉,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及利用西方墨點法及聚合酶連鎖反應實驗來探討其可能的分子機轉。 在進行實驗後,我們發現大腦中動脈血管阻塞/再灌流模式動物實驗模式所造成之缺血性腦中風,會導致數個與發炎及細胞凋亡相關的因子表現,如:iNOS、HIF-1α、TNF-α、caspase-3,並可能經由這些因子的表現而造成腦部傷害的形成及擴大,而單獨給予葛根素(50mg/kg),可有效的減少因為大腦中動脈血管阻塞/再灌流引發缺血性腦中風所造成的腦部傷害,而給予葛根素外同時給予clopidogrel(20mg/kg),對腦部傷害的改善情形,並無明顯的增益效果。 |
英文摘要 | Antiplatelet drugs were utilized on preventing vascular diseases include myocardial infection (MI), stroke and cardiovascular diseases. 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. Clopidogrel was a highly potent inhibitor of ADP-induced platelet aggregation. Furthermore, it inhibited collagen or thrombin induced platelet aggregation, because of the involvement of released ADP as an amplifier of the aggregation induced by other agonists. Clopidogrel proved more effective than asipirin in reducing subsequent ischaemic strokes and other vascular events in a large clinical trail with recent ischaemic strokes or other antherosclerosis diseases. A primary component of most functional extracts of Pueraria lobata is puerarin. It was reported that puerarin (100mg/kg) could reduced infracted site after ischemia reperfusion in rats. The inhibitory mechanism of puerarin may through apoptosis inhibition to protect neuron cells. Puerarin could prevent ischaemic strokes through neuron protection. Therefore, we want to investigate whether puerarin combined with clopidogrel provide substantial increase in efficacy on cerebral ischemic infarction. We will use the model of middle cerebral artery (MCA) occlusion/reperfusion to study the effect of two drugs on infarct size, behavioral test, lipid peroxidation, neurological deficit, grip test, and investigation of molecular mechanisms through western bloting and reverse transcription polymerase chain reaction (RT-PCR) after transient MCAO in rats. We found ischemia reperfusion injury that caused brain injury may through several inflammation and apoptosis related factor such as iNOs, HIF-1α, TNF-α and caspase-3 expression. Pretreatment of puerarin (50mg/kg) could reduced ischemia reperfusion induced brain injury, and combined therapy of puerarin (50mg/kg) and clopidogrel (20mg/kg) did not show obvious benefit as compared to treatment of puerarin (50mg/kg) alone. |
本系統之摘要資訊系依該期刊論文摘要之資訊為主。