SD大鼠阿霉素慢性心力衰竭模型的建立与评价

Establishment and evaluation of adriamycin-induced chronic heart failure model in SD rats

目的通过尾静脉注射阿霉素建立SD大鼠慢性心力衰竭模型,并对其进行评价。方法成年♂SD大鼠随机分为两组:正常对照组(CON组,n=8)和阿霉素心力衰竭组(ADR组,n=20)。ADR组尾静脉注射阿霉素2 mg.kg-1,每周1次,计6周,累积剂量达12 mg.kg-1;CON组静脉注射等容积0.9%的氯化钠溶液,周期同前。末次注射2周后图测定心功能包括左心室舒张末内径(LVEDD)和收缩末内径(LVESD)并计算左室短轴缩短率(LVFS)及射血分数(LVEF);病理学检测包括HE及VG染色观察心肌组织形态学改变;ELISA法测定血浆BNP浓度。结果与CON组相比,ADR组大鼠LVEDD和LVESD增加,LVFS和LVEF明显下降(P<0.01);HE染色可见部分心肌纤维断裂,心肌间质炎细胞浸润;VG染色心肌间质胶原容积分数(CVF)及心肌血管周围胶原面积(PVCA)明显增加(P<0.01),心肌纤维化明显;血浆BNP水平升高(P<0.01)。结论静脉多次注射阿霉素能够导致SD大鼠心功能降低和心肌组织形态学改变,成功建立可靠的非缺血性慢性心力衰竭模型。

Aim To establish and evaluate an adriamycin-induced chronic heart failure model by tail vein injection in Sprague Dawley（SD） rats.Methods Adult male SD rats were randomly divided into two groups：the control group（CON,n=8） and the adriamycin-induced heart failure group（ADR,n=20）.All rats in ADR group received 2 mg·kg-1adriamycin as an intravenous tail vein infusion once a week for 6 weeks at a total dose of 12 mg·kg-1;meanwhile in CON group,rats received an equal volume of 0.9% sodium chloride intravenously.Transthoracic echocardiography was performed to observe cardiac function including left ventricular end-diastolic diameter（LVEDD） and end-systolic diameter（LVESD） and calculate left ventricular fractional shortening（LVFS） and ejection fraction（LVEF） 2 weeks later after the last injection.The pathological change was analyzed by HE and Van Gieson（VG） stain.The plasma concentration of brain natriuretic peptide（BNP） was determined by euzymelinked immunosorbent assay（ELISA）.Results Compared with CON group,LVEDD and LVESD were increased in ADR group,and LVFS and LVEF were significantly decreased（P0.01）.The pathological changes by HE stain in ADR group were part of myocardial fiber fracture and myocardial periacardial inflammatory infiltration.Collagen volume fraction（CVF） and perivascular circumferential collagen area（PVCA） by VG stain were significantly higher（P0.01） than CON group.And the level of plasma BNP was significantly higher than that in CON group.Conclusions Adriamycin at a multiple intravenous dose of 2.0 mg·kg-1 can be used to establish a reliable model of non-ischemia chronic heart failure in SD rats and lead to a decline in ventricular function and pathological changes.