학술대회 안내 사전등록 안내 초록등록 안내 초록등록/관리 숙박및교통 안내


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ǥ : ǥ ȣ - 500243   343 
Cardioprotective effect of antioxidant, thioctacid(α-lipoic acid), in myocardial ischemia-reperfusion injury : Induction of endogenous antioxidants and activation of PI3K-Akt and Erk 1/2 kinase cascades
원광대학교 순환기내과¹ , 생리학교실²
오석규¹, 김민선² , 윤경호¹ , 김재권¹ , 김남호¹ , 정진원¹
Background : Reactive oxygen species(ROS) have a important role in development of reperfusion injury. Mitogen-activated protein(MAP) kinases are activated by ROS during reperfusion. α-Lipoic acid(LA) has been reported to reduces ischemia-reperfusion injury in isolated-perfused rat hearts. In this study, we examined whether treatment of LA before reperfusion can prevent myocardial reperfusion injury by measurement of myocardial infarct size, ROS generation and activity of MAP kinases during reperfusion in vivo. Methods : We used Spague-Dawley rats(250-300 gram) in occlusion of a left anterior descending coronary artery for 45 minutes followed by reperfusion for 45 minutes. We administered 25 mg/kg(n=5), 50 mg/kg(n=5), and 100 mg/kg(n=5) of LA in left ventricle directly 10 minutes before reperfusion in LA treatment group and 0.5ml of normal saline in control group. The ratio of the infarct area to the ischemic area at risk was measured by propidium iodide(PI) fluorescence. The generation of ROS was observed by the fluorogenic probe, dichlorodihydrofluorescein(CM-H2DCFDA). MAP kinases(ERK 1/2 and JNK 1/2) activity was measured by Western blot analysis at 10 and 30 minutes after reperfusion. Results : The ratio of the infarct area to the ischemic area at risk of 25 mg/kg LA was smaller than that of control group(28.8±11.4% vs 53.4±10.4%, p<0.0001), but that of 50 mg/kg(52.4±6.9%, p=0.633) and 100 mg/kg(50.1±20.5%, p=0.402) LA were not difference compared to control group. Treatment of LA before reperfusion was slightly reduced the generation of ROS in ischemic myocytes. pERK 1/2 activity which has anti-apoptotic effect was significantly higher in treatment of LA compared to control group at 10 and 30 minutes after reperfusion(p<0.05, p<0.05). pJNK 1/2 activity which has apoptotic effect was significantly lower in treatment of LA compared to control group at 10 and 30 minutes after reperfusion (p=NS, p<0.05). Conclusion : Our study suggested that treatment of LA before reperfusion was effective in reducing myocardial reperfusion injury in vivo. This effect appears to be related to the reduction of ROS generation, activation of pERK 1/2 and suppression of pJNK 1/2.


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