咪达普利对舒张功能不全大鼠心功能的保护与减轻心肌线粒体损伤有关
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广东省自然科学基金(4000526)


The Protective Effect of Imidapril on Cardiac Function and Mitochondrion of Rat with Diastolic Heart Failure
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    摘要:

    目的探讨咪达普利对舒张功能不全心力衰竭大鼠心脏功能保护作用的机制。方法30只雄性SD大鼠,随机分为对照组、模型组、用药1组、用药2组和用药3组共5组。采用腹主动脉缩窄建立舒张功能不全心力衰竭模型,对照组只开腹和分离腹主动脉。3个用药组大鼠术后分别灌胃给予咪达普利1.5 mg/(kg.d)、3或6 mg/(kg.d);对照组和模型组大鼠灌胃给予同等量的生理盐水共4周。4周末心脏B超检测心功能,颈动脉插管记录血流动力学变化,取心脏称重,计算与体重的比例,分光光度计检测线粒体丙二醛、超氧化物歧化酶和谷胱甘肽过氧化物酶变化,电镜检测心肌线粒体超微结构改变。结果心脏超声心动图发现舒张功能不全心力衰竭组大鼠室间隔和左心室后壁厚度、E/A比值明显增高,血流动力学检测发现收缩压、舒张压、左心室收缩压、左心室舒张期末压升高,左心室松弛时间常数延长,左心室内压最大下降速率下降,心脏指数和左心室质量指数增加。咪达普利使增加的室间隔和左心室后壁厚度、E/A、收缩压、舒张压、左心室收缩压、左心室舒张期末压、心脏指数和左心室质量指数降低,左心室松弛时间常数缩短,左心室内压最大下降速率升高,随着咪达普利剂量的增加,改变的程度越明显。线粒体功能检测发现,舒张功能不全心力衰竭组大鼠超氧化物歧化酶和谷胱甘肽过氧化物酶下降,丙二醛增加,电镜观察发现心肌细胞肌丝排列不整齐、线粒体肿胀及空泡化等线粒体损伤;咪达普利减轻线粒体结构和功能损伤。结论咪达普利通过减轻心肌细胞和线粒体损伤改善舒张功能不全心力衰竭大鼠的心脏功能。

    Abstract:

    Aim To study the protective effect of imidapril on cardiac function and mitochondrion of rats with diastolic heart failure. Methods 30 SD rats were randomly divided into 5 groups:control group, DHF group,A1.5mg,A3mg,and A6mg group.DHF model was produced by abdominal aortic coarctation in the rats in the operating group.The rats in A1.5mg-A6mg groups were given with imidapril [1.5,3,and 6 mg/(kg·d)] by intragastric administration for 4 weeks,the others were treated with equal isotonic NaCl.After 4 weeks,cardiac function and hemorheology was assessed by echocardiography and catheterization.Specimens were taken and ventricular mass were measured.The level of malonaldehyole(MDA),superoxidedismutase(SOD),and glutathioneperoxidase(GSHPx) were detected by spectrophotometer.Ultra structure changes in myocardium were observed under electrion microscopy. Results In DHF group,PW,IVS,LVM,E/A ratio,SBP,DBP,LVSP,LVEDP,and MDA were increased,Tau was prolonged,LV-dp/dtmax,SOD and GSHPx was decreased.The myocardium damage including abnormality of myofilament arrangement,mitochondrial swelling and vacuolization were showed.Compared with DHF group,increased E/A ratio,IVS,PW,LVM,SBP,DBP,LVSP,LVEDP and MDA were decreased,prolonged Tau was shorted,decreased LV-dp/dtmax,SOD and GSH-Px were increased in treated groups.The myocardium damage was ameliorated in treated groups too.The protective effect of Imidapril on heart was increased according to the increasing dose of it. Conclusion Imidapril improve cardiac function in rats with DHF by ameliorating the damage of myocardic cell and mitochondrion.

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唐惠芳,吴书林,邓春玉,张文昶,邝素娟.咪达普利对舒张功能不全大鼠心功能的保护与减轻心肌线粒体损伤有关[J].中国动脉硬化杂志,2006,14(11):940~944.

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  • 收稿日期:2006-04-03
  • 最后修改日期:2006-08-06
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