京尼平通过SIRT3/SOD2改善小鼠缺血/再灌注后心脏功能

目的 研究栀子果实的主要药效成分京尼平对小鼠心肌缺血/再灌注（myocardial ischemia/reperfusion，MI/R）损伤后心功能的影响及其机制。 方法 将C57BL/6小鼠心脏冠状动脉左前降支结扎/放松建立小鼠心肌缺血/再灌注模型；通过Miller导管和心脏超声检测心脏功能，TUNEL染色检测细胞凋亡，western blot检测SIRT3、SOD2及凋亡相关分子的表达量。 结果 与Sham组相比，给予京尼平（50 mg/kg）显著改善了MI/R小鼠心脏功能，减轻了心肌细胞的凋亡及减少了凋亡相关分子的表达量。进一步研究表明，京尼平提高了SIRT3的表达量并降低了乙酰化SOD2水平。给予SIRT3的抑制剂3-TYP后，京尼平改善MI/R小鼠心脏功能、减轻心肌细胞凋亡及减少凋亡相关分子表达量的效果受到了显著抑制。 结论 京尼平具有改善MI/R后小鼠心脏功能和减轻心肌细胞的凋亡的作用，其机制与京尼平提高SIRT3的表达量和降低SOD2的乙酰化程度有关。

Genipin protects against myocardial ischemia/reperfusion through SIRT3/SOD2

AIM To examine the effect of genipin on cardiac function after myocardial ischemia/reperfusion (MI/R) injury in mice and its underlying mechanism. METHODS MI/R injury model was established by ligation/relaxation of the left anterior descending coronary artery in C57BL/6 mice. Cardiac function was detected by Miller catheter and echocardiography. Cell apoptosis was detected by TUNEL staining. SIRT3, SOD2 and apoptosis-related molecules were detected by Western blot. RESULTS Compared with Sham group, administration of genipin significantly improved the cardiac function of MI/R mice and reduced the cardiac apoptosis and the expressions of apoptosis-related molecules. Further results showed that genipin increased the expression of SIRT3 and decreased the ratio of Ac-SOD2/SOD2. Administration of 3-TYP, an inhibitor of SIRT3, blocked the effect of genipin on improving the cardiac function of MI/R mice, reducing the cardiac apoptosis and reducing the expressions of apoptosis-related molecules. CONCLUSION Genipin improves the cardiac function of MI/R mice and reduces the apoptosis and the expression of apoptosis-related molecules through, at least partially, upregulation of SIRT3 and downregulation of SOD2 acetylation.