樟芝併用aspirin在大鼠暫時性腦血管梗塞之作用探討

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題名:	樟芝併用aspirin在大鼠暫時性腦血管梗塞之作用探討 Study of Antrodia camphorata combined with aspirin in transient MCAO
作者:	余孟哲 Yu, Meng-Che
貢獻者:	醫學科學研究所馮琮涵
關鍵詞:	暫時性腦血管梗塞;大鼠;樟芝;阿斯匹靈 MCAO;Rat;Antrodia camphorat;aspirin
日期:	2014-06-30
上傳時間:	2019-09-03 11:43:27 (UTC+8)
摘要:	腦中風是國內十大死因之第三位，且目前尚無藥物能夠有效治療腦中風，因此腦中風患者的照護時常帶給社會龐大負擔。台灣原生種真菌—樟芝，因富含大量三萜類而被作為保健食品，廣泛應用於肝病或是癌症的輔助治療上；近來亦有研究指出，樟芝在腦中風及心血管疾病的預防及治療上可能具有其功效，但其機轉及可能的副作用尚不清楚。Aspirin 為目前臨床上最常使用來治療或預防腦中風的藥物，但是許多研究皆指出 aspirin具有出血性副作用的風險；因此尋找有效治療腦中風的藥物，研究其機轉及降低治療藥物的出血性副作用，為目前腦中風研究上的重要課題。另外，台灣有許多病患會同時併用西藥及保健食品來治療和預防中風，因此我們除了分別探討樟芝及 aspirin在缺血性腦中風的療效外，亦進一步探討此兩者併用對於治療缺血性腦中風的交互作用，以及觀察其出血性副作用。本實驗利用線栓引發中大腦動脈梗塞動物模式，探討缺血/再灌流 24小時後，分別管餵樟芝 (0.25 及 0.75 g/kg)、aspirin (5 mg/kg)或併用兩者 2個月，藥物對缺血性腦中風的影響。研究結果發現樟芝不論單獨或併用 aspirin皆顯著降低缺血性傷害，並且加速改善其神經行為功能。另外，樟芝 (0.75 g/kg)單獨或併用 aspirin (5 mg/kg)能有效降低缺血性中風所引起的 iNOS、HO-1、Bax 及 actived caspase-3表現。利用電子自旋共振儀，我們也發現樟芝 (40 mg/ml)具有清除氫氧自由基 (OH˙)的能力。除此之外，不論單獨餵食樟芝或併用 aspirin皆無發生顱內出血、蜘蛛膜下腔出血和胃出血等副作用，凝血酶原時間亦無顯著影響。本篇論文證明不論單獨給予樟芝 (0.25 及 0.75 g/kg)、aspirin (5 mg/kg)或併用兩者皆能透過抑制細胞凋亡、降低氧化壓力、降低缺血性腦傷害及改善神經功能，而具有神經保護作用，並且各組都未表現出血性的副作用。因此本論文提供了樟芝在治療缺血性腦中風臨床應用上的科學化依據，相信不論是單獨使用樟芝或者併用其他抗血小板藥物來治療缺血性中風，在未來皆為值得進一步研究探討的課題。 Stroke is the third leading cause of mortality in Taiwan. So far, there are no better medicine to treat stroke. Therefore, this disease always results a heavy social burden in taking care of patient.Antrodia camphorata, a native species of fungi in Taiwan,is considered as a dietary supplement due to the enrichment of triterpenoid. It has been widely used in liver disease or even cancertreatment. Recently, some studies also indicated that Antrodia camphorata maybe beneficial on the prevention and treatment of stroke and cardiovascular diseases,but the mechanism and possible side effect are not well known yet.Aspirin is the most commonly used drug in clinic for the treatment or prevention of stroke, but many studies indicated aspirin has a higher risk of hemorrhage. Thus, to drug in the remedy of stroke with better effectiveness and less adverse effect is an important issue of stroke research.On the other hand, there are many patients in Taiwan concurrently takewestern medicine and health food to treat and prevent of stroke.Therefore, in the present study, wetreated aspirin combined with Antrodia camphoratato investigate their protective efficacy after ischemic stroke. In addition, we alsoestimate hemorrhagic side effects. In this study, our results showed that treatment of Antrodia camphorata (0.25 or 0.75 g/kg) in the absence or presence of aspirin (5 mg/kg) by oral gavages daily after transient MCAO for two months markedly reduced infarct size and improved neurologic functions.We further observed several proteins, including iNOS, HO-1, Bax, and caspase-3, which are associated with brain injury. Our data revealed that Antrodia camphorate markedly decrease the expression of these proteins. Antrodia camphorata In addition, treatment of Antrodia camphorata 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 given alone Antrodia camphorata (0.25 and 0.75 g / kg), aspirin (5 mg / kg) or with both has a potent neuroprotective activity. This activity is mediated, at least in part, through inhibition of apoptosis, oxidative stress, resulting in a reduction of infarct volume and improvement in neurobehavior in rats with focal cerebral ischemia without hemorrhaging side effects. Therefore, Antrodia camphorata may represent high therapeutic potential and safe for treatment of ischemic stroke.
描述:	碩士指導教授-馮琮涵共同指導教授-許準榕委員-張釗監委員-楊志豪委員-林冠宏
資料類型:	thesis
顯示於類別:	[醫學科學研究所] 博碩士論文

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