安石榴苷减轻心肌缺血/再灌注损伤的作用及机制研究  

Protective effects of punicalagin against myocardial ischemia-reperfusion injury and underlying mechanism

作　　者：丁铭格[1] 贾敏[2] 屈引贤[1] 韩宏程[1] 李蔚渤[1] 付锋[2] 雷海录[3] DING Ming-ge;JIA Min;QU Yin-xian;HAN Hong-cheng;LI Wei-bo;FU Feng;LEI Hai-lu(Department of Geriatrics,Xi ＇an Central Hospital.Xi＇an 710004,Shaanxi,China;Department of Physiology,Fourth Military Medical University,Xi＇an 710032,Shaanxi,China;Department of Hepa-tological Surgery,451 Hospital of PLA,Xi＇an 710054,Shaanxi,China)

机构地区：[1]西安市中心医院老年病科,陕西西安710004 [2]第四军医大学生理学教研室,陕西西安710032 [3]解放军451医院肝胆外科,陕西西安710054

出　　处：《心脏杂志》2018年第5期503-507,共5页Chinese Heart Journal

基　　金：国家自然科学基金项目资助(81600235;81670354)

摘　　要：目的探讨安石榴甙(PUN)预先处理对心肌缺血/再灌注损伤(MI/RI)的作用及其机制。方法选取成年雄性SD大鼠,PUN 30 mg/(kg·d)生理盐水灌胃7 d后,建立心肌缺血再灌注(MI/R)模型。采用右侧颈总动脉插管检测心脏功能,用伊文思蓝和氯化三苯基四氮唑(TTC)双染检测心梗面积,测定血清肌酸激酶同工酶(CK-MB)和乳酸脱氢酶(LDH)活性反映心肌损伤,原位末端标记(TUNEL)法检测心肌细胞凋亡,比色法检测心肌丙二醛(MDA)含量和超氧化物歧化酶(SOD)的活性,蛋白免疫印迹检测磷酸腺苷活化蛋白激酶(AMPK)表达及磷酸化。结果 PUN预先处理可改善MI/R后的心脏功能,减少心梗面积和心肌细胞凋亡,降低CK-MB和LDH的活性,降低心肌氧化应激,增加AMPK磷酸化(均P <0. 05或P <0. 01),而使用AMPK抑制剂(compound c)可阻断PUN对MI/R的保护作用(P <0. 05或P <0. 01)。结论 PUN预先处理可减轻MI/RI,其机制可能与其激活AMPK有关。AIM To investigate the effects of punicalagin （PUN） on myocardial ischemia-reperfusion （MI/R） injury and underlying mechanisms. METHODS PUN [30 mg/（ kg·d） ] was intragastrically administered to male Sprague-Dawley rats for 7 d before operation. MI/R was induced by ligating the left anterior descending coronary artery for 30 rain and subsequent reperfusion for 3 h. Cardiomyocyte apoptosis was determined by a terminal deoxynucleotidyl nick-end labeling （TUNEL） assay. The antioxidant enzyme superoxide dismutase （SOD） activities and malonaldialdehyde （MDA） levels in myocardial homogenates were determined spectrophotometrically. Outcome measures included cardiac functions, myocardial injury, oxidative stress and levels of phosphorylated adenosine monophosphate-activated protein kinase （AMPK） protein. RESULTS PUN pretreatment conferred cardioprotective effects against MI/R injury by improving cardiac functions, limiting infarct size, reducing serum creatine kinase-MB and lactate dehydrogenase activities, and suppressing cardiomyocyte apoptosis. Moreover, PUN pretreatment inhibited I/R-induced myocardial oxidative stress as evidenced by decreased malonaldialdehyde formation and increased super- oxide dismutase activity （ both, P 〈 0. 05 or 0. 01 ）. Furthermore, PUN pretreatment increased AMPK phosphorylation in I/R hearts. AMPK inhibitor compound c blunted PUN-mediated cardioprotectionagainst MI/R injury （P 〈0. 05 or 0. 01 ）. CONCLUSION These results indicate that PUN pretreatment protects against I/R-induced myocardial injury via activation of AMPK.

关 键 词：安石榴苷 心肌缺血/再灌注损伤 氧化应激 细胞凋亡 磷酸腺苷活化蛋白激酶 

分 类 号：R282.7[医药卫生—中药学]