白藜芦醇对小鼠阿霉素性心肌损伤的保护作用及机制

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。

Protective effect and mechanism of resvera on adriamycin-induced cardiotoxicity in mice

Aim To observe the protective effect and mechanism of resvera on adriamycin-induced cardiotoxicity. Methods The cardiotoxicity was induce by adriamycin (ADM) intraperitoneal injection (ip. 15 mg·kg-1). Then the protective effect of pretreatment of resvera on injured cardiomyocyes was observed. Results Compared with the normal control group, ADM decreased the amplitude of ECG′s QRS complex (P<0.01), increased the incidence of arrhythmia (to 60%), injured myocardial ultrastructure, increased the activity of LDH, levels of NO and MDA in serum, decreased the activity of SOD, and increased the expression of p53 (P<0.01). Compared with ADM group, 5, 10, 15 mg· kg-1 resvera decreased levels of LDH, NO and MDA, increased SOD activity, recovered the amplitude of QRS complex,decreased the incidence of arrhythmia and p53 expression (P<0.01 or P<0.05) in concentration-dependent manner, and lightened the myocardial ultrastructure injury. Resvera showed no significant change on normal mice except increasing the activity of SOD in serum. Conclusion Resvera had protective effect on adriamycin-induced cardiotoxicity. The mechanism may be related to its enhancing myocardial SOD activity, inhibiting myocardial lipid peroxidation and apoptosis.