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標題: | 沙立朴酚對血清素在心血管作用之影響 The Effects of Thaliporphine on Cardiovascular Responses to Serotonin |
作者: | Ching-Chia Chang Chien 張簡敬家 |
指導教授: | 蘇銘嘉(Ming-Jai Su) |
關鍵字: | 沙立朴酚,血清素,缺血再灌流, Thaliporphine,serotonin,ischemia reperfusion, |
出版年 : | 2006 |
學位: | 碩士 |
摘要: | Serotonin (5-HT) 被認為會經由引發血小板凝集、冠狀動脈收縮,以及增加心肌細胞自由基而加重心臟在缺血再灌流後造成的傷害。 Thaliporphine在過去已被證實在活體大鼠上能夠減少心臟缺血再灌流造成的傷害,並且能減少經LPS引發敗血症的大鼠多重器官傷害的程度,並提高其存活率。另外,本實驗發現在離體灌流心臟上,Thaliporphine與5-HT皆會增加冠狀動脈流速,而Thaliporphine 1 μM 則有輕微抑制5-HT增加冠狀動脈流速的作用。在離體灌流心臟的冠狀動脈結紮再灌流模式中,於結紮前灌流Thaliporphine 0.1 μM 或5-HT 10 μM 可以減少心肌壞死的比率。在離體去內皮的主動脈上,1 μM Thaliporphine能部分拮抗5-HT引發的收縮反應 (使EC50由0.88 ± 0.34 μM 提高到6.41 ± 0.70 μM )。在大鼠富含血小板血漿中,Thaliporphine有抑制5-HT 合併 collagen 所引發的血小板凝集作用的趨勢。而在離體心肌組織中,Thaliporphine輕微抑制5-HT 1 μM 所引起左心房及右心房收縮力增強作用。然而在此實驗中所發現Thaliporphine影響5-HT心血管作用是否對Thaliporphine 在冠狀動脈阻塞再灌流之活體動物實驗之心臟保護作用有貢獻,仍有待進一步的釐清。 Serotonin (5-HT) is believed to aggravate ischemia reperfusion injury by ways of inducing platelet aggregation, coronary artery constriction, and increasing the oxidative stress in cardiomyocytes. In the past years, Thaliporphine has been demonstrated to protect rat hearts from post-ischemia reperfusion injury in vivo. It also increases survival rate as well as attenuates multiple organ injury in LPS-induced endotoxaemia in vivo. In the present study, we found that Thaliporphine and 5-HT increased coronary flow in a dose dependent way, but 1 μM Thaliporphine attenuated the serotonin-induced increase of coronary flow. Thaliporphine 1 μM attenuated vasoconstriction response to serotonin in rat de-endothelium thoracic aorta (EC50 was shifted from 0.88 ±0.34 μM to 6.41 ± 3.70 μM), and Thaliporphine 10-5 uM suppressed aggregation response to 5-HT 10-5 uM plus collagen 3 ug/ml in rat platelet rich plasma.In Langendorff perfused rat hearts, Thaliporphine 0.1 uM or 5-HT 10 uM pretreatment decreased infarct size in coronary occlusion/reperfusion hearts. Whether the inhibition of serotonin-induced vasoconstriction or platelet aggregation contribute to the cardioprotective efficacy of Thaliporphine in ischemia/reperfusion animals remains to be clarified. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/32186 |
全文授權: | 有償授權 |
顯示於系所單位: | 藥理學科所 |
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