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研究生:許玲維
研究生(外文):Ling-Wei Hsu
論文名稱:桃仁承氣湯併用aspirin在大鼠自體血栓引發腦血管梗塞之活性作用探討
論文名稱(外文):Study of Tao-Ren-Cheng-Qi-Tang combined with aspirin in thromboembolic MCAO rat model
指導教授:許準榕
指導教授(外文):Joen-Rong Sheu
口試委員:顏茂雄馮琮涵
口試日期:2013-07-04
學位類別:碩士
校院名稱:臺北醫學大學
系所名稱:醫學科學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:中文
論文頁數:102
中文關鍵詞:缺血性中風桃仁承氣湯
外文關鍵詞:ischemic strokeMCAOTRCQT
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中風是國內十大疾病死因之第三位,且造成社會龐大負擔。目前為止,尚未有任何一種藥物能夠完全治療中風。在台灣,有許多病人在西藥治療之外,併用傳統中藥治療和預防中風。因此探討中西藥併用於中風,其交互作用和副作用風險等為重要課題。在中國大陸,桃仁承氣湯長期被中醫用於治療缺血性中風。另一方面,aspirin臨床上用於預防缺血性中風,但有出血風險。本篇實驗併用傳統中藥桃仁承氣湯和西藥aspirin,探討兩者併用對於治療缺血性中風之作用,以及觀察其出血性副作用。
實驗利用自體血栓引發中大腦動脈梗塞動物模式,術後24小時每天管餵桃仁承氣湯(0.5 g/kg)併用aspirin (5 mg/kg)一個月和三個月,結果顯示桃仁承氣湯不論單獨或併用aspirin皆顯著降低缺血性傷害,並且加速改善其神經行為功能,但aspirin則無此效果。除此之外,桃仁承氣湯併用aspirin有效降低缺血性中風導致TNF-α、JNK、Bax、caspase-3表現和腦組織切片TUNEL染色。另外桃仁承氣湯(0.2-0.4 mg/ml)隨著劑量增加有效降低血小板凝集,在小鼠斷尾凝血試驗管餵桃仁承氣湯(860 mg/kg)一週亦有效延長凝血所需時間。利用ESR發現桃仁承氣湯(0.3、0.7、1.3 mg/ml)具有清除氫氧自由基(OH˙)的能力。除此之外,在探討副作用的實驗,如顱內出血、蜘蛛膜下腔出血和胃出血等,皆無出血情形,凝血酶原時間並無顯著增加。
本篇實驗證明桃仁承氣湯不論單獨或併用aspirin皆有神經保護作用,藉由抑制發炎反應、細胞凋亡、氧化壓力和血小板活化而降低缺血性腦傷害、改善神經功能,並且無出血性副作用。在本論文研究證實桃仁承氣湯的確是一有效治療缺血性腦中風且值得進一步研究的中藥方劑。
Stroke is the third leading cause of mortality in Taiwan, and it makes a heavy social burden. So far, there are no better medicines to treat stroke. In Taiwan, a large amount of patient often use modern medicine combined with traditional Chinese medicine (TCM) to treat or prevent stroke. Thus, to investigate the efficiency of TCM combined with medicine is important and warrant study. In China, Tao-Ren-Cheng-Qi Tang (TRCQT) has been used to treat ischemic stroke by traditional Chinese physicians. On the other hand, aspirin is routinely used to prevent ischemic stroke in clinic. Nevertheless, many studies indicate that taking aspirin will increase the risk of excessive bleeding. In this study aims to investigate whether treatment of TRCQT combined with aspirin can improve focal cerebral ischemia in a rat model of thromboembolic stroke, and to evaluate its major side effect of hemorrhaging.
Our results showed that treatment of TRCQT (0.5 g/kg) combined with aspirin (5 mg/kg) or TRCQT alone by oral gavages daily after thromboembolic MCAO for one month and three months markedly reduced infarct size and improved neurologic functions, but aspirin alone had no effects. There are increasing in TNF-α, JNK, Bax, and caspase-3 protein expressions associated with brain injury, and these protein expressions were determined by western blot analysis, which obviously reduced by treatment of TRCQT. In addition, treatment of TRCQT combined with aspirin presented the anti-apoptotic effects by a TUNEL assay. Furthermore, TRCQT (0.2-0.4 mg/ml) inhibited collagen induced platelet aggregation in a concentration dependent manner. Treatment of TRCQT (860 mg/kg) prolonged the tail vein bleeding time in a mouse model. Using electron spin resonance (ESR), TRCQT (0.3, 0.7, 1.3 mg/ml) markedly reduced hydroxyl radical (OH•) in the H2O2/DMSO system, indicating that TRCQT has anti-oxidant activity. In addition, treatment of TRCQT combined with aspirin or not didn’t have side effects of hemorrhage such as intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), gastric bleeding (GB), and prothrombin time (PT).
In conclusion, this study demonstrates that TRCQT possesses a potent neuroprotective activity. This activity is mediated, at least in part, through inhibition of inflammatory responses, apoptosis, oxidative stress and platelet activation, resulting in a reduction of infarct volume and improvement in neurobehavior in rats with focal cerebral ischemia without hemorrhaging side effects. Therefore, TRCQT may represent high therapeutic potential and safe for treatment of ischemic stroke.
中文摘要-------------------------------------------------- 1
英文摘要-------------------------------------------------- 2
縮寫------------------------------------------------------ 3
緒論------------------------------------------------------ 6
實驗材料------------------------------------------------- 18
實驗方法------------------------------------------------- 24
實驗結果------------------------------------------------- 37
實驗討論------------------------------------------------- 49
結論----------------------------------------------------- 63
未來展望------------------------------------------------- 64
參考圖表------------------------------------------------- 65
結果附圖------------------------------------------------- 72
參考文獻------------------------------------------------- 90
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