Objective: To study the protective effects of resveratrol (RSV) on cardiac function in rats with high altitude hypobaric hypoxia and its mechanisms. Methods: Thirty-six rats were randomly divided into control group, hypobaric hypoxia group (HH) and hypobaric hypoxia + RSV group (HH+RSV) according to the random number, 12 rats in each group. Rats in the HH and HH+RSV groups were subjected to chronic long-term high altitude hypobaric hypoxia intervention for 8 weeks in a hypobaric chamber at a simulated altitude of 6 000 m for 20 h / d. The rats of HH + RSV were fed with RSV at a dose of 400 mg/(kg·d). The rats were tested once a week for body weight and twice a week for food intake. Before execution, the rats were tested by blood cell analyzer for routine blood parameters and echocardiogram for cardiac function parameters in each group. The routine blood indexes of each group were measured by blood cell analyzer, the cardiac function indexes of each group were measured by echocardiography, myocardial hypertrophy was evaluated by HE staining, myocardial tissue reactive oxygen levels were evaluated by dihydroethidium (DHE) staining. Oxidative stress was evaluated by serum and myocardial tissue total antioxidant capacity (T-AOC), superoxide dismutase activity (SOD) and malondialdehyde (MDA) content. Results: Compared with the C group, the body mass and food intake of rats were decreased significantly (P＜0.05) in HH group, while compared with the C group, RSV had no significant effects on the body mass and food intake of rats in the HH+RSV group (P＞0.05). Compared with the C group, the levels of erythrocytes and hemoglobin of rats in the HH group were increased significantly (P＜0.05), while the platelet concentration was decreased significantly(P＜0.05); compared with the HH group, the erythrocyte and hemoglobin levels were decreased significantly (P＜0.05) and platelet concentration was increased significantly(P＜0.05) in rats of the HH+RSV group. Compared with the C group, the cardiac coefficient, myocardial fiber diameter and thickness were significantly increased in the HH group (P＜0.05); compared with the HH group, the cardiac coefficient and myocardial fiber thickness were significantly decreased in the HH+RSV group (P＜0.05). Echocardiographic analysis showed a significant increase in ventricular wall thickness (P＜0.05) and a significant decrease in ejection fraction and cardiac output (P＜0.05) in the HH group compared with the C group, and a significant decrease in ventricular wall thickness and a significant improvement in cardiac function (P＜0.05) in the HH+RSV group compared with the HH group. The results of DHE staining showed that myocardial tissue reactive oxygen levels were increased significantly in the HH group compared with the C group (P＜0.05); myocardial tissue reactive oxygen levels were significantly restored in the HH+RSV group compared with the HH group (P＜0.05). The oxidative/antioxidant results showed that the serum and myocardial T-AOC and SOD activities were decreased significantly (P＜0.05) and the MDA level was increased significantly (P＜0.05) in the HH group compared with the C group; the serum and myocardial T-AOC and SOD activities were increased significantly (P＜0.05) and the MDA level was decreased significantly(P＜0.05) in the HH+RSV group compared with the HH group. Conclusion: Long-term plateau hypobaric hypoxia exposure leads to myocardial hypertrophy and reduced cardiac function in rats. Resveratrol intervention significantly improves myocardial hypertrophy and cardiac function in rats caused by altitude hypobaric hypoxia exposure, which is closely related to reducing of reactive oxygen species and improving myocardial oxidative stress levels.
目的: 研究白藜芦醇(RSV)对高原低压低氧大鼠心功能的保护作用及机制。方法: 将36只大鼠按照随机数字法分为对照组(Control, C)、低压低氧组(HH)和低压低氧+RSV组(HH+RSV),每组12只。HH组和HH+RSV组大鼠在低压氧舱模拟海拔6 000 m,20 h / d进行慢性长期高原低压低氧干预8周,RSV灌喂浓度为400 mg/(kg·d)。大鼠每周检测1次体重、2次摄食量,大鼠处死前采用血细胞分析仪检测各组血常规指标、超声心动图检测各组大鼠心功能指标,采用HE染色评价心肌肥厚情况,采用二氢乙啶( DHE)染色评价心肌组织活性氧水平,采用血清及心肌组织总抗氧化能力(T-AOC)、超氧化物歧化酶活性(SOD)、丙二醛(MDA)含量评价氧化应激情况。结果: 与C组相比,HH组大鼠体质量和摄食量显著降低(P＜0.05);而与HH组相比,HH+RSV组大鼠体质量及摄食量无显著影响(P＞0.05)。血常规结果显示,与C组相比,HH组大鼠红细胞和血红蛋白显著升高(P＜0.05),血小板浓度显著降低(P＜0.05);与HH组相比,HH+RSV组大鼠红细胞和血红蛋白水平显著降低(P＜0.05),血小板浓度显著升高(P＜0.05)。与C组相比,HH组心脏系数、心肌纤维直径和厚度显著增大(P＜0.05);与HH组相比,HH+RSV组大鼠心脏系数和心肌纤维厚度显著下降(P＜0.05)。超声心动图分析显示,与C组相比,HH组大鼠心室壁厚度显著增加(P＜0.05),射血分数及心输出量显著降低(P＜0.05);与HH组相比,HH+RSV组大鼠心室壁厚度显著降低,心脏功能显著改善(P＜0.05)。DHE染色结果显示,与C组相比,HH组大鼠心肌组织活性氧水平显著升高(P＜0.05);与HH组相比,HH+RSV组大鼠心肌组织活性氧水平明显恢复(P＜0.05)。氧化抗氧化结果显示,与C组相比,HH组大鼠血清及心肌T-AOC、SOD活性显著降低(P＜0.05),MDA含量显著升高(P＜0.05);与HH组相比,HH+RSV组大鼠血清及心肌T-AOC、SOD活性显著升高(P＜0.05),MDA含量显著降低(P＜0.05)。结论: 长期高原低压低氧暴露导致大鼠心肌肥厚、心功能下降,白藜芦醇干预可以显著改善高原低压低氧暴露导致的大鼠心肌肥厚及心功能降低,这与其降低活性氧改善心肌氧化应激水平密切相关。.
Keywords: Resveratrol; echocardiography; hypobaric hypoxia; myocardial hypertrophy; rats.