培哚普利联合厄贝沙坦治疗大鼠扩张型心肌病近期和远期疗效

Short- and long-term therapeutic effects of combination therapy with perindopril and irbesartan in a rat model of dilated cardiomyopathy

目的:探讨培哚普利联合厄贝沙坦治疗扩张型心肌病(DCM)大鼠的近、远期疗效。方法:腹腔注射阿霉素建立大鼠DCM模型。实验大鼠分4组:A组(n=14)为正常大鼠,B组(n=26)为DCM大鼠,均无药物干预;C(n=24),D(n=24)组均为DCM大鼠,其中C组予以培哚普利2mg/(kg·d)灌胃,D组予以培哚普利1mg/(kg·d)联合厄贝沙坦25mg/(kg·d)灌胃。酶联免疫吸附法检测血浆脑利钠肽(BNP)水平;检测血钾、血肌酐水平;心肌HE染色后进行病理评分;记录干预过程各只大鼠存活期。结果:药物干预3周后,D组BNP水平低于C组(P<0.05);各组干预前后血钾、血肌酐水平差异无统计学意义(P>0.05);与B组比较,C和D组心肌病理损害均减轻(P<0.01),而C与D组间心肌病理损害的差异无统计学意义(P>0.05)。对数秩检验显示:C组存活期短于D组(P<0.05);Cox回归分析显示:联合用药或单用培哚普利为延长生存期因素,联合用药作用更明显。结论:培哚普利联合厄贝沙坦治疗DCM大鼠,在改善心功能及远期预后方面优于单用培哚普利,2种方案均能减轻心肌病理损害且未见血钾、血肌酐升高不良反应。

Objective To evaluate the short-term, and long-term therapeutic effects of combination therapy with perindopril and irbesartan in a rat model of dilated cardiomyopathy （DCM）. Methods Sprague-Dawley rats were administered adriamycin intraperitoneally to develop DCM. Grouping of rats： Group A contained normal rats, and Group B contained DCM rats. Both Group A and B were not given drug treatment. Group C and D contained DCM rats, however, Group C was administered perindopril 2 mg/（ kg·d ） while Group D was administered perindopril 1 mg/（ kg·d） and irbesartan 25 mg/（ kg·d ）. Brain natriuretic peptide （ BNP ） was determined by enzyme linked immunosorbent assay ; plasma potassium and creatinine were measured ; the pathological lesions of cardiac muscle tissues were evaluated after HE staining; and the survival time of each rat during the intervention was recorded. Results After the three-week intervention, the plasma concentrations of BNP in Group D were lower than those in Group C （ P 〈 0.05 ） ; In each group, plasma concentrations of potassium and creatinine showed no significant differences between pre-intervention and post-intervention （ P 〉 0.05 ） ; pathological lesions of cardiac muscle tissues in both Group C and D were attenuated compared with those in Group B （ P 〈 0.01 ） , but pathological lesions of cardiac muscle tissues showed no significant differences between Group C and Group D （P 〉 0.05 ）. Log-rank test showed that the life span of Group C was shorter than that of Group D （ P 〈 0.05 ） ; Cox regression analysis showed that both combination therapy and monotherapy with perindopril could prolong the survival time, but the effect of combination therapy was more obvious. Conclusion Combination therapy with perindopril and irbesartan in a rat model of DCM can more effectively improve the cardiac function and long-term prognosis than those monotherapy with perindopril. Both these two treatment plans can attenuate the pathological lesions of cardiac muscle tissues, without elevating the concentrations of plasma potassium and creatinine.