金丝桃苷通过调节自噬水平减轻心肌梗死小鼠心脏及胸主动脉的损伤

目的：探讨金丝桃苷（hyperoside, Hyp）对心肌梗死小鼠心脏和胸主动脉的保护作用及可能的机制。方法：通过永久结扎小鼠冠状动脉左前降支构造心梗模型，然后将小鼠分为假手术组（生理盐水，0.1 mg/10 g）、模型组（生理盐水，0.1 mg/10 g）、金丝桃苷低、中、高浓度组（金丝桃苷，9、18、36 mg/kg）、福辛普利组（福辛普利，15 mg/kg）、金丝桃苷高剂量+3-MA组（金丝桃苷，36 mk/kg；3-MA，30 mg/kg）。药物治疗两周后检测小鼠心重指数、心电图、心功能变化、血清氧化应激水平，另外还检测小鼠胸主动脉重塑以及血管内皮功能变化。结果：心肌梗死模型组小鼠与假手术组小鼠相比，心重指数增加（P<0.01）、心电图QRS波宽度上升、高度降低（P<0.01）、心腔变大（P<0.01）、血清氧化应激水平升高（P<0.01）、胸主动脉重塑、内皮功能紊乱（P<0.01）。给予不同剂量的金丝桃苷以及福辛普利治疗两周后，小鼠心电图异常有所恢复，血清氧化应激水平降低，胸主动脉重塑及内皮功能紊乱得到一定程度的改善（P<0.05或P<0.01）。而金丝桃苷联合自噬抑制剂3-MA治疗后能够逆转金丝桃苷对心脏和血管的保护作用（P<0.05或P<0.01）。 结论：金丝桃苷对心肌梗死小鼠的心脏损伤和胸主动脉重塑以及内皮功能紊乱具有一定的保护作用，3-MA能够逆转金丝桃苷对心梗小鼠心血管的保护作用。提示金丝桃苷对心梗小鼠的心血管保护作用机制可能与金丝桃苷提高了心肌梗死后小鼠心脏自噬水平并抑制氧化应激损伤有关。

Hyperoside ameliorates the injury of heart and thoracic aorta in mice with myocardial infarction by regulating autophagy pathway

AIM: To explore the protection of Hyperoside (Hyp) on heart and thoracic aorta in mice with myocardial infarction (MI) as well as its potential mechanism. METHODS: The MI model was generated by a ligation on the left anterior descending coronary artery. The mice were then randomly divided into sham group (saline, 0.1 mg/10 g), model group (saline, 0.1 mg/10 g), Hyp-low, moderate and high concentration groups (Hyp, 9, 18 and 36 mg/kg), Fosinopril group (Fosinopril, 15 mg/kg), and Hyp-high concentration + 3-MA group (Hyp, 36 mg/kg; 3-MA, 30 mg/kg). The mice were treated with Hyp and Fosinopril for two weeks, and then the changes of heart weight versus body weight (HW/BW), electrocardiogram (ECG) remodeling, cardiac function, oxidative stress level in serum, thoracic aorta remodeling and endothelial function were investigated. RESULTS: In the model group, the HW/BW was elevated (P<0.01). The width of QRS in ECG was elevated, as a company with the reduction of height of QRS (P<0.01). The echocardiography assay showed that the cardiac cavity was enlarged (P<0.01). The oxidative stress level in serum was enhanced (P<0.01). The thoracic aorta remodeling and endothelial dysfunction became more serious (P<0.01). After being treated with different concentrations of Hyp and fosinopril for two weeks, the changes above were reserved (P<0.05, P<0.01). Co-treatment with 3-MA, an autophagy inhibitor, suppressed the protective effects of Hyp on impaired hearts and vessels (P<0.05, P<0.01). CONCLUSION: Hyp has protective prospects on injured heart and thoracic aorta remodeling, as well as endothelial dysfunction in MI mice; 3-MA, an autophagy inhibitor, can reverse the cardiovascular protection of Hyp. The mechanism may be explained that Hyp can elevate autophagy level in heart, which further weaken oxidative injury in MI mice.