和厚朴酚对心肌梗死小鼠心脏的保护作用

Protective effect of honokiol on the heart of mice after myocardial infarction

目的研究和厚朴酚对心肌梗死(MI)小鼠心脏的保护作用。方法小鼠随机分为假手术组(sham组)、MI组及和厚朴酚(HK)组(MI+HK组)。通过结扎小鼠冠状动脉左前降支建立MI模型,腹腔注射给药的方式进行HK干预。术后28 d时用小动物心脏超声及小鼠心脏压力容积导管法检测小鼠心脏功能,Masson染色检测小鼠心肌梗死后心脏纤维化,TUNEL法检测小鼠心肌细胞的凋亡,蛋白质免疫印记检测纤维化关键分子(Tgfb1、Col1a1和Acta2)和凋亡相关分子(Bax/Bcl-2)。结果与sham组相比,MI组小鼠的左心室射血分数(LVEF)显著下降(P<0.001),左心室舒张末压力(LVEDP)显著升高(P<0.001),等容收缩期左心室内压力上升的最大速率(dP/dt_(max))显著降低(P<0.001);与MI组相比,和厚朴酚组小鼠LVEF显著提高(P<0.05),LVEDP显著下降(P<0.001),左心室等容收缩期dP/dt_(max)显著升高(P<0.05)。与sham组相比,MI组小鼠的心脏质量与胫骨长度比值(HW/TL)显著升高(P<0.01),梗死远端纤维化指数显著升高(P<0.001),梗死边缘组织心肌细胞凋亡显著增加(P<0.001),心脏纤维化关键分子Tgfb1、Col1a1和Acta2的转录水平显著升高(P<0.001),凋亡相关分子Bax/Bcl-2的比值也显著升高(P<0.001);与MI组相比,和厚朴酚组小鼠HW/TL显著降低(P<0.05),梗死远端纤维化指数显著下降(P<0.001),梗死边缘组织心肌细胞凋亡受到显著抑制(P<0.001),心脏纤维化关键分子Tgfb1、Col1a1的转录水平显著下降(均P<0.05),以及Acta2的转录水平显著下降(P<0.01),凋亡相关分子Bax/Bcl-2的比值也有降低(P<0.05)。结论和厚朴酚能够改善心肌梗死后小鼠心脏功能,抑制梗死边缘区域细胞凋亡及降低纤维化程度,发挥心肌梗死后小鼠心脏保护作用。

Objective To explore the protective effect of honokiol on mice heart after myocardial infarction(MI).Methods Mice were randomly divided into sham group,MI group and honokiol group(MI+HK).The mouse model of MI was established by ligation of the left anterior descending coronary artery.The cardiac function of the mouse was detected by echocardiography and mouse cardiac pressure volume catheter,the fibrosis of the heart was detected by Masson staining,the apoptosis was detected by TUNEL staining,and the fibrosis-and apoptosis-related molecules were detected by Western blot.Results Compared with sham group,the left ventricular ejection fraction(LVEF)was significantly decreased in MI group(P<0.001),the left ventricular end-diastolic pressure(LVEDP)was significantly increased(P<0.001),and the maximum rate of intraventricular pressure rise(dP/dt_(max))was significantly decreased(P<0.001).Compared with MI group,LVEF was significantly increased in MI+HK group(P<0.05),LVEDP was decreased(P<0.001)and dP/dt_(max) was significantly increased(P<0.05).Compared with sham group,the heart weight to tibia length ratio(HW/TL)was significantly increased in MI group(P<0.01),the fibrosis index at the distal region of the infarct was significantly increased(P<0.001),the apoptosis was significantly increased(P<0.001),the transcription levels of key molecules of cardiac fibrosis Tgfb1,Col1a1 and Acta2 were significantly increased(P<0.001),and the ratio of apoptosis-related molecule Bax/Bcl-2 was also significantly increased(P<0.001).Compared with MI group,HW/TL of mice was significantly decreased(P<0.05),the fibrosis index at the distal region of the infarction was significantly decreased(P<0.001),the myocardial cell apoptosis in the infarct border region was significantly inhibited(P<0.001),the cardiac fibrosis was significantly reduced(P<0.001),the transcription levels of Tgfb1,Col1a1 and Acta2 were significantly decreased(P<0.05),and the ratio of apoptosis-related molecule Bax/Bcl-2 was also decreased in MI+HK group(P<0.05).Conclusion Honokiol could improve the cardiac function of mice,inhibit the apoptosis of cells in the border region and reduce the degree of fibrosis,and exert a protective effect on the heart of mice after MI.