表没食子儿茶素没食子酸酯调控自噬抗心肌缺血再灌注损伤  

Epigallocatechin gallate alleviates myocardial ischemia reperfusion injury by adjusting autophagy

作　　者：李春凤[1] 孙瑶[1] 简洁[1] 

机构地区：[1]桂林医学院药学院,广西桂林541004

出　　处：《中国新药与临床杂志》2015年第6期471-475,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：2011年广西高等学校优秀人才资助项目(桂教人[2011]40号)

摘　　要：目的研究表没食子儿茶素没食子酸酯(EGCG)调控自噬抗心肌缺血再灌注损伤的作用。方法64只SD大鼠随机分为假手术、模型、3-甲基腺嘌呤(3-MA,15 mg·kg-1)、EGCG(20 mg·kg-1)四组(n=8),各组于造模前20 min舌下静脉给予相应试剂,采用左冠状动脉前降支结扎法制备大鼠心肌缺血再灌注模型,按试剂盒说明书检测缺血30 min及缺血30 min-再灌注1 h各组肌酸激酶同工酶(CK-MB)、总抗氧化力(T-AOC)、诱导型一氧化氮合酶(i NOS)的含量,以Western-blot法检测心肌微管相关蛋白轻链3蛋白-Ⅱ(LC3-Ⅱ)、Beclin-1、雷帕霉素靶蛋白(m TOR)的表达。结果自噬在心肌缺血期即发生,再灌注时进一步加强;与模型组相比,EGCG组心肌缺血-再灌注不同时段的T-AOC能有效提高,CK-MB及i NOS的含量降低,LC3-Ⅱ、Beclin-1蛋白表达下调,m TOR蛋白表达上调(P<0.05);与3-MA组相比,EGCG组大鼠血清i NOS及CK-MB降低,T-AOC含量提高,LC3-Ⅱ、Beclin-1蛋白表达下调,m TOR蛋白量上调(P<0.05)。结论 EGCG对心肌的保护作用可能与提高抗氧化力,降低i NOS有关;EGCG预处理可能通过短暂诱导心肌缺血期自噬发生,抑制再灌注时段自噬过度表达而减轻心肌缺血再灌注损伤。AIM To study the effects of epigallocatechin gallate （EGCG） on adjusting autophagy in myocardial ischemia reperfusion injury. METHODS Sixty- four SD rats were randomly divided into control, model, 3 - methyladenine （ 3 - MA, 15 ·kg^-1） and EGCG （ 20 mg ·kg^-1） group （ n = 8）. Corresponding reagents were given through the sublingual veins 20 rain before the model building in each group. Ischemia 30 rain or ischemia 30 min/reperfusion 1 h, while myocardial ischemia reperfusion model was established by ligating left anterior descending coronary artery. To contents of creatine kinase-myoglobin （CK-MB）, total antioxidative capacity （T-AOC） and inducible nitric oxide synthase （iNOS） in serum were determined according to the kits. The protein expression of microtubule-associated protein 1 light chain 3 （LC3- Ⅱ ）, Beclin- 1 and mammalian target of rapamycin （mTOR） was observed by Western- blot. RESULTS Autophagy occurred in myocardial ischemia period, then enhanced in reperfusion time. Compared with the model group, EGCG could effectively improve T-AOC, decreased CK-MB and iNOS （P 〈 0.05）. Meanwhile, EGCG down-regulated the protein expression of LC3- Ⅱ and Beclin-1, as well as up-regulated mTOR protein expression （P 〈 0.05）. Compared with the 3-MA group, EGCG reduced the contents of CK-MB and iNOS, increased the level of T-AOC （P 〈 0.05）. It descended LC3- Ⅱ and Beclin- 1 protein expression and improved the protein expression of roTOR （P 〈 0.05）. CONCLUSION EGCG pretreatment reduces myocardial ischemia/reperfusion injury maybe by influencing on relating factors of autophagy, promoting autophagy occurrence during ischemia period and inhibiting it in reperfusion.

关 键 词：儿茶素 心肌缺血 再灌注损伤 自噬 

分 类 号：R972[医药卫生—药品] R965[医药卫生—药学]