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目的研究白藜芦醇(Res)对阿霉素(ADM)诱导的心肌损伤的保护作用及机制。方法一次性腹腔注射ADM(15mg·kg-1),建立小鼠阿霉素急性心肌损伤模型,并观察白藜芦醇预防性给药的保护作用。结果与正常对照组相比,ADM可使小鼠心电图QRS波电压幅度下降(P<0.01),心律失常率发生达60%;心肌超微结构损伤明显;血清中MDA、NO含量及LDH活性升高,SOD活性降低;p53蛋白表达升高(P<0.01)。与ADM损伤组相比,5、10、15mg·kg-1白藜芦醇呈剂量依赖性降低血清LDH活性和MDA、NO含量,增加SOD活性;减少QRS波电压下降幅度和心律失常发生率;下调p53蛋白表达(P<0.01或P<0.05);减轻电镜下心肌超微结构损伤。白藜芦醇对正常小鼠仅升高SOD活性,对其余指标无明显影响。结论Res对阿霉素性心脏损伤具有保护作用,其机制可能与其增强心肌SOD活力、抗脂质过氧化和抑制心肌细胞凋亡有关。
Objective To study the protective effect and mechanism of resveratrol (Res) on adriamycin (ADM)-induced myocardial injury. Methods One-week intraperitoneal injection of ADM (15 mg·kg-1) was used to establish an acute myocardial injury model of adriamycin in mice and to observe the protective effect of resveratrol on prophylactic administration. Results Compared with the normal control group, ADM could decrease the amplitude of QRS voltage of the electrocardiogram (P<0.01), arrhythmia rate of 60%, and ultrastructural damage of myocardium. The content of MDA, NO, and LDH activity in serum increased. High, SOD activity decreased; p53 protein expression increased (P<0.01). Compared with the ADM injury group, 5, 10, and 15 mg·kg-1 resveratrol dose-dependently reduced serum LDH activity, MDA, NO content, and increased SOD activity; decreased QRS wave voltage decrease rate and incidence of arrhythmia; Down-regulation of p53 protein expression (P<0.01 or P<0.05); reduced ultrastructure damage of myocardium under electron microscope. Resveratrol only increased SOD activity in normal mice and had no significant effect on other indicators. Conclusion Res has a protective effect on adriamycin-induced cardiac injury. Its mechanism may be related to its enhancement of myocardial SOD activity, anti-lipid peroxidation and inhibition of myocardial cell apoptosis.