实验性心力衰竭大鼠模型的建立及评价

Establishment and evaluation of the experimental congestive heart failure model in rats

目的建立实验性心力衰竭大鼠模型,并对其进行评价。方法35只雄性Wistar大鼠随机分两组:正常对照组(CON组,n=10)和心力衰竭模型组(CHF组,n=25),CHF组采用阿霉素2.5 mg/kg尾静脉注射,每周一次,连续10 w,建立CHF大鼠模型。12 w时采用超声和血流动力学检测评价其心功能,放免法检测血浆肿瘤坏死因子-α、血管紧张素Ⅱ及醛固酮水平,氯胺T法检测羟脯氨酸及胶原含量,苦味酸天狼星红染色进行左室胶原特异染色及定量分析,计算胶原容积分数(CVF),并进行HE染色,观察其组织学变化。结果CHF组大鼠死亡率为40%(10/25),CON组无死亡。与CON组相比,CHF组大鼠左室舒张末期内径(LVEDD)及收缩末期内径(LVESD)增加,心功能明显下降,表现为左室短轴缩短率(FS)、二尖瓣环收缩期长轴方向峰值运动速度(Vs)、左室内压最大上升速率(+dp/dtmax)、左室内压最大下降速率(-dp/dtmax)明显降低,左室舒张末期压(LVEDP)升高(P<0.01);CHF组血浆肿瘤坏死因子-α、血管紧张素Ⅱ及醛固酮水平升高(P<0.01),心肌羟脯氨酸及胶原含量较CON组增加(P<0.01);苦味酸天狼星红染色显示CHF组左室胶原明显增加,胶原容积分数(CVF)明显增高(P<0.01);病理学结果证实符合心肌病样改变。结论阿霉素多次小剂量静脉注射能导致大鼠发生心脏间质纤维化及心脏舒缩功能降低,可成功建立实验性心力衰竭大鼠模型。

Objective To establish and evaluate the rat model of experimental congestive heart failure （CHF）. Methods Thirty five adult male Wistar rats were randomly divided into control group （received an equivalent volume of 0.9% saline alone intravenously） and CHF group （n = 25 ） （injected with adriamycin at a dose of 2. 5 mg/kg intravenously once a week for 10 weeks）. Echocardiographic and hemodynamics measurements were obtained at 12 weeks after treatment. Then left ventricular （LV） samples were collected. The plasma concentrations of TNF-, Ang Ⅱ and aldosterone were determined by immunoradiometric assay. The hydroxyproline and collagen content were determined by the methods of chloramines T. The expression and distribution of collagen in LV were investigated with picric acid-sirius red staining techniques. Semi-quantitative analysis was used to evaluate collagen volume fraction （CVF）. The pathological change was analyzed by histological hematoxylin-eosin staining. Results The cumulative mortality in CHF group was 40%. Compared to the control group, LV end- diastolic diameter （LVEDD）, LV end systolic diameter （LVESD） and LV end-diastolic pressure （LVEDP） were significantly increased in CHF group （all P 〈0. 01 ）. Fraction shortening （FS） , Vs, ＋ dp/dtmax and -dp/dtmax and indices of LV contractile function were significantly reduced in CHF group （all P 〈0. 01 ）. The level of TNF-, Ang Ⅱ and aldosterone were higher in CHF group than those in control group （P 〈0. 01 ）. The hydroxyproline and collagen content were increased in CHF group （both P 〈 0.01 ）. LV myocardial collagen increased and myocardial fibrosis occurred, LV collagen volume fraction （CVF） increased significantly by picric acid-sirius red staining. The pathological examnation was consistent with histological changes of CHF. Conclusions Chronic adruinistration of adriamycin at a low dose intravenously to rat could result in LV myocardial fibrosis and heart falure, and the rat model of experimental congestive heart failure is established successfully.