降香通过抗氧化应激改善后负荷增加型心衰小鼠的心脏功能

目的:研究降香对后负荷增加引起的的心脏功能下降的保护作用及其机制。方法:雄性C57小鼠30只,随机分为三组,分别给予假手术(sham)、主动脉弓结扎(Transverse aortic constriction,TAC)手术和主动脉弓结扎手术降香治疗(TAC+DO)处理。通过灌胃给药4周,随后超声检测心脏功能、四腔心切片观察心肌重构,RT-PCR检测左心室αMHC、βMHC的m RNA表达、相应试剂盒心肌总抗氧化能力(TAOC)和丙二醇(MDA)含量。结果:同sham组相比,TAC组射血分数(EF),αMHC m RNA水平和TOAC均显著降低,且左室舒张末内径(LVIDd)、左室舒张期后壁厚度(LVPWd)、左室质量(LV mass)、心肌质量/胫骨长度(HW/TL)及β及β度、MDA均显著增加。同TAC组相比,DO组射血分数(EF),αMHC m RNA水平和TOAC均显著增加,且左室舒张末内径(LVIDd)、舒张末室间隔厚度(IVSd)、左室质量(LV mass)、心肌质量/胫骨长度(HW/TL)及βMHC、MDA均显著下降。在离体培养的心肌细胞,H_2O_2可显著增加细胞内ROS含量,给予降香或TEMPOL处理均可减轻H_2O_2诱导的氧化应激并增加心肌细胞存活率。结论:降香可通过降低氧化应激抑制线粒体分裂并改善后负荷增加型心衰的心脏功能。

Dalbergiae Odoriferae Reduces Oxidative Stress and Improves Cardiac Dysfunction in Pressure Overload-induced Failing Heart

ABSTRACT Objective: To explore the protective effect of Dalbergiae Odoriferae(DO) on cardiac dysfunction in pressure over- load-induced failing heart in mice and the underlying mechanisms. Methods: C57 mice (male, 6 weeks) were used for induction of HF through pressure overload. Pressure overload was produced by transverse aortic constriction (TAC) as described previously. After surgery, the mice were randomized to given vehicle or DO for 4 weeks. An in vitro study was performed on cultured cardiomyocytes sub- jected to control, H₂O₂, H₂O₂+DO and H₂O₂+DO, H₂O₂+TEMPOL. Results: Cardiac ejection fraction(EF) was decreased and myocardial remodeling was significant in response to pressure overload, along with cardiac TOAC level was dropped and malondialdehyde (MDA) production were significantly elevated, which led to dampened cardiac function and myocardial remodeling. DO treatment significantly reduced MDA production and improved cardiac dysfunction. Importantly, incubation of cardiomyocytes with H₂O₂ significantly induced cell death. Treatment with DO or ROS Scavenger TEMPOL reduced oxidative stress induced by H₂O₂ and increased cell viability. Conclusion: DO treatment alleviates oxidative stress in the progress of heart failure, which improves cardiac dysfunction and normalized myocardial remodeling.