臺灣博碩士論文加值系統

中文摘要
1.Cinnamphilin (Cinn)是由樟科植物Cinnamonum Philippinense抽提出來的屬non-alkaloid的成分，之前的研究結果顯示在老鼠的單一心室細胞膜電位鉗定實驗中， Cinn可以抑制鈉電流和鈣電流，且Cinn有抑制瞬間外流鉀電流Ito之作用，所以可以延長動作電位(APD50) 。Cinn在離體心臟缺血再灌流所誘發之心室心律不整有恢復的作用。
2.當心臟缺血再灌流會誘發心室心律不整，期間大量自由基的產生，氧化壓力與內生性抗氧化能力的失衡是造成心臟損傷的重要因素。
3.除了電生理的作用之外，Cinn具有中度的抗氧化能力，濃度在18.4mM能清除較穩定自由基 (DPPH)，但對超氧自由基的清除能力不佳。Quinidine為一典型的抗心律不整藥物，但無抗氧化作用，對DPPH與超氧自由基皆無法有效清除，因此本實驗主要在探討同樣具ion channels blocker的天然植物抽出成份Cinn與quinidine，前者具中度抗氧化作用，而後者無，比較二者在活體動物實驗中對缺血再灌流所誘發的心室心律不整以及心肌的傷害，Cinn是否能優於quinidine。
4.本實驗將大鼠經由腹腔注射預給Cinn或quinidine 1 mg、 3 mg、 10 mg/kg ，再將左冠狀動脈結紮造成急性缺血接著再灌流來誘發心律不整，評估Cinn 和quinidine 在下列三種動物實驗模式中，抗心律不整以及對心肌的保護作用。
(i)缺血5分鐘再灌流30分鐘。
(ii)缺血30分鐘。
(iii)缺血30分鐘再灌流2小時。
5.Cinn對活體動物缺血5分鐘再灌流30分鐘所誘發的心室心律不整，與死亡率皆無法產生保護的作用，而quinidine在1 mg/kg和10 mg/kg可以減少VF的發生率和VF duration。
6.在活體動物缺血30分鐘所誘發心室心律不整的實驗結果顯示Cinn 10 mg/kg可以縮短VF duration和降低死亡率而quinidine在1 mg/kg、10 mg/kg可有效縮短VF duration，和降低死亡率。
7.在心肌梗塞方面Cinn 3 mg/kg與Qunidine 10 mg/kg可減少心肌梗塞面積，分別從53.8±5.1%減少為36±5.9%，53.5±4.2%減少為40.6±3.5%。
8.整體而言quinidine在活體動物缺血5分鐘再灌流30分鐘實驗模式中，Qunidine抗心律不整的作用還是優於Cinn，而在減少心肌梗塞方面Cinn比quinidine具相當或較強之保護作用。

Abstract
1. Cinnamophilin (Cinn), which is non-alkaloid in nature, was found to have the capability to reverse coronary ligation-reperfusion induced ventricular arrhythmia to regular rhythm in isolated Langendorff perfused rat heart models. This action was proved to be related with its prolongation of APD50 and inhibition of potassium outward current and sodium inward current in isolated rat cardiac cell.
2. In animals, reperfusion of ischemic heart is associated with an excessive generation of free radicals which results in imbalance between oxidative stress and available endogenous antioxidant and becomes a major factor for reperfusion arrhythmia and cardiac injury.
3. Since Cinn was found to have diphenyl-2-picrylhydrazyl (DPPH) scavenging activity with an IC0.2 of 18.4 mM in this study, we decided to examine the protective activity of Cinn in ischemia or ischemia-reperfusion animals and compare with quinidine which was known to have similar antiarrhythmic activity as Cinn in coronary ligation-reperfusion rat hearts.
4. In this study, the left main coronary artery of the anesthetized rat was occluded by the following procedures
(i)5 min occlusion followed by 30 min reperfusion.
(ii)30 min occlusion.
(iii)30 min occlusion followed by 2 hr reperfusion.
Animals were pretreated with Cinn or quinidine at dose between 1mg to 10 mg/kg (injected intraperitoneally). Mortality and the severity of ischemia and ischemia/reperfusion —induced arrhythmia were compared.
5. In animals subjected to 5 min occlusion and 30 min reperfusion , Cinn failed to reduce the mortality ,the incidence and duration of ventricular tachycardia (VT) and ventricular fibrillation (VF) .Quinidine , however, exerted significant efficacy in reducing the mortality and severity of VF at 1 mg/kg and 10 mg/kg.
6. In animals subjected to 30 min occlusion, Cinn at 10 mg/kg significantly reduced mortality and severity of VF . Quinidine at 1mg to 10 mg/kg effectively reduced the mortality and severity of VT and VF.
7. Though the severity of VF in animals subjected to 30 min occlusion followed by 2 hr reperfusion was reduced by 10 mg/kg Cinn and 1mg/kg or 10 mg/kg quinidine, the infarct size (expressed as percentage of occluded zone) was only partly reduced by 3 mg/kg Cinn and 10 mg/kg quinidine from 53.8±5.1% to 36±5.9% and 53.5±4.2% to 40.6±3.5% , respectively.
8. We conclude that quinidine have better antiarrhythmic activity and mortality prevention efficacy especially in animals subjected to 5 min ischemia followed by 30 min reperfusion .The efficacy of Cinn in prevention of myocardial infarction is comparable or stronger than quinidine.

目 錄
縮寫對照 …………………………………………….. 1
中文摘要……………………………………………… 3
英文摘要……………………………………………… 5
第一章緒論………………………………………… 8
第二章實驗材料與方法…………………………… 20
第三章實驗結果…………………………………… 27
第四章討論………………………………………… 34
第五章結論………………………………………… 38
圖表…………………………………………………….. 39
參考文獻……………………………………………….. 67

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