培哚普利对慢性心力衰竭大鼠心肌能量代谢及超微结构的影响

Effects of peidolapril on myocardial energy metabolism and the ultrastructural changes in chronic heart failure rats

目的研究培哚普利对异丙肾上腺素（ISO）诱导的慢性心力衰竭（CHF）大鼠心肌能量代谢和超微结构的影响。方法55只雄性SD大鼠随机（随机数字法）分为对照组（C组）和模型组。模型制备采用皮下多点注射ISO法，4周后模型组再随机（随机数字法）分为未治疗组（M组）和培哚普利治疗组（P组）。平均治疗5周后进行二维心脏超声检查，测定心肌组织中ATP、ADP、AMP、乳酸（LA）含量、肌浆网Ca^2＋．ATP酶（SERCA）活性以及进行病理形态学的观察。结果与未治疗组相比，培哚普利治疗组大鼠左室射血分数（EF）、左室短轴缩短率（FS）分别提高了3．25％和7．33％。光镜和电镜结果显示，培哚普利治疗组心肌损伤程度较模型组明显减轻。与对照组相比，未治疗组大鼠心肌ATP、AMP、TAN（总腺苷）和LA含量均显著下降（P〈0．05），但培哚普利治疗组大鼠心肌ADP、AMP、ATP／ADP和TAN（总腺苷）含量与对照组相比差异无统计学意义（P〉0．05）。与未治疗组相比，培哚普利治疗组大鼠心肌SERCA活性提高了16．41％（P〉0．05）。结论培哚普利能够改善心力衰竭大鼠心肌能量代谢、病理和超微结构。

Objective To study the effects of perindopril on myocardial energy metabolism and uhrastructural changes in rats with chronic heart failure （CHF） induce by isoproterenol. Methods Totally 55 male SD rats were randomly （random number） divided into two groups, namely control group （Group C） and CHF model group. The CHF rat models were made by subcutaneous injection of isopreteronol （IS0） in doses of 20 mg · kg-1 · d-1 , 10mg · kg-1 ·d-1 and 5 mg/kg/d for successive 3 days and then 3 mg · kg-1 · d-1 for 9 days. Four weeks later, the rats in CHF model group were randomly further divided into two subgroups, namely untreated subgroup （group M ） and perindopril treated subgroup （group P ）. After treatment for five weeks in average, echocardiography and myocardial pathology examination carried out to assess the cardiac function and structure changes of these rats. The levels of ATP, ADP, AMP, lactic acid （LA） and sarcoplasmic reticulum Ca2＋ -ATPase （SERCA） activity in myocardium were determined by enzymatic reaction. Results Compared with rats in group M, the ejection fraction of left ventricle （EF） and fractional shortening of short axis of left ventricle （FS） of the rats in group P increased by 3.25% and 7. 33% , respectively. Compared with rats in group C, the myocardial ATP, AMP, TAN （total adenosine） and LA significantly decreased in rats of group M. There were no significant differences in the levels of ADP, AMP, ATP/ADP and TAN between group C and group P （P 〉 0. 05）. Compared with rats in group M, the myocardial SERCA activity increased by 16.41% in rats of group P. The myocardial injury found under microscope and electronic microscope was ameliorated by treatment with peidolapril in rats of group P in comparison with rats of group M. Conclusions Perindopril can improve myocardial energy metabolism, and lessen the pathological changes of ultrastructure, enhancing the cardiac function of rats with CHF induced by ISO.