摘要
目的观察心力衰竭时自噬相关蛋白的表达以及抑制自噬对心力衰竭的影响,探讨自噬在心力衰竭发病过程中的作用。方法实验分为对照组(control)、心力衰竭组(HF)和3甲基腺嘌呤(3MA)组。心力衰竭组采用腹主动脉缩窄术制备大鼠心力衰竭动物模型。3MA组给予心力衰竭大鼠自噬特异性抑制剂3MA 15 mg/kg,连续两周。采用心导管术检测大鼠左室舒张末压(LVEDP)、左室等容收缩期压力上升最大速率+dp/dtmax、左室等容舒张期压力下降的最大速率-dp/dtmax。用Western blot法检测心肌组织自噬相关蛋白beclin-1、cathepsin D的表达。结果1)心力衰竭组LVEDP较对照组显著增加(P<0.05),±dp/dtmax较对照组显著降低(P<0.05)。使用3MA组LVEDP较心力衰竭组显著降低(P<0.01),±dp/dtmax较心力衰竭组显著增加(P<0.01,P<0.05)。2)心力衰竭组心肌组织自噬相关蛋白beclin-1和cathepsin D表达较对照组显著增加(P<0.05),而3MA组beclin-1、cathepsin D的表达较心力衰竭组显著减少(P<0.05)。结论心肌细胞自噬在心力衰竭发病过程中发挥着致病作用。
Objective To investigate the pathogenic role of cardiomyocyte autophagic death in heart failure. Methods Thirty SD rats were randomized into three groups： control group, heart failure group and 3-methylade- nine （3 MA） group. In heart failure group, heart failure was induced by abdominal aorta constriction. The 3 MA, a specific inhibitor on autophagy was used in a heart failure model of rats induced by overload pressure. We ex- amined the heart function of rats in three groups. In addition, we analyzed the expression of autophagy associated protein, beclin-1 and cathepsin D in rat hearts using Western blot. Results The expression of beclin-1 and ca- thepsin D in the hearts of heart failure rats were significantly increased as compared those in control group （ P 〈 0.05 ）. 3MA significantly improved cardiac function and significantly downregulated the expression of beclin 1 and cathepsin D in abdominal aorta constriction-induced failing heart. Conclusions Autophagic cardiomyocyte death plays an important role in the pathogenesis of heart failure in rats induced by pressure overload.
出处
《基础医学与临床》
CSCD
北大核心
2014年第8期1023-1026,共4页
Basic and Clinical Medicine
基金
国家自然科学基金(81102585
81373570)
广东省自然科学基金(S2011040003510)
中国博士后科学基金(20110490871)
