培哚普利减轻阿霉素对大鼠心脏毒性的研究

Alleviation of Cardiotoxicity of Adriblastina by Perindopril in Rats

目的:观察阿霉素(adriblastina,ADR)造成大鼠心室功能不同程度损害时,心肌内血管紧张素Ⅱ(Ang Ⅱ)等的改变及培哚普利对其影响。方法:给大鼠腹腔注射ADR 1 mg/kg,5天1次,依累计量分为A(3次)、B(5次)及C(8次)3组,D组仅注射生理盐水;培哚普利干预组则分别于注射2(A组)、4(B组)及6次(C组)后开始于饮水中喂培哚普利(1 mg·kg^(-1)/日)。于停给ADR第10天麻醉下测心功能,留取动脉血及心肌标本用放射免疫法测Ang Ⅱ等。每小组动物均为7只。结果:ADR造成心功能轻中度损害时,血浆Ang Ⅱ和醛固酮已显著升高,与对照组比较,P均<01.1,而心肌中Ang Ⅱ的增高较缓。当心功能进一步损害时,心肌Ang Ⅱ进一步升高,而血浆Ang Ⅱ不再增加。培哚普利可明显遏制心肌和血浆Ang Ⅱ的增加(与ADR组比较,P均<0.05),心室功能损害亦较轻;当ADR剂量继续增加和延长使用后,改善心室功能的作用略有减弱。结论:培哚普利对大鼠能明显阻抑ADR引起心肌Ang Ⅱ的增高并减轻对心功能的损害。

Objective:To study changes of the renin-angiotensin-aldosterone system (RAS) and the effect of perindopril on different degrees of heart damage induced by adriblastina (ADR) in rats. Methods:For the ADR group (n=7 in each), ADR (1 mg/kg once every 5 days, ip) was given 3 times (group A), 5 times (group B) and 8 times (group C) to rats while normal saline was given to controls (group D, n= 7);for the perindopril intervention group (n=7 in each),after ADR injection of 2 times in group A, 4 times in group B and 6 times in group C, perindopril (1 mg·kg^(-1)/d) was given in drinking water. At the 10 th day after the last ADR injection, cardiac function was estimated under anesthesia, Ang Ⅱ and aldosterone of arterial blood and the myocardium were determined by RIA. Results:Plasma Ang Ⅱ and aldosterone levels significantly increased (p<0.01 vs. control) in the earlier period of ADR administration while the ventricular function had only mild damage. Myocardial Ang Ⅱ incrased further when the heart damage lasted for a certain period of time, meanwhile ,plasma Ang Ⅱ showed no further increase. Perindopril could significantly inhibit the increase of myocardial and plasma Ang Ⅱ (all p<0.05 vs. ADR group), and improve heart function as well,but the effects of improving heart function decreased as ADR was given in larger doses. Conclusion: Perindopril could significantly inhibit adriblastina-induced increase of myocardial angiotensin-Ⅱ and protect against heart damage.