主动脉弓缩窄术和腹腔注射IPH致小鼠慢性心衰两种模型的比较和评价

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目的:比较和评价主动脉弓缩窄术与腹腔注射盐酸异丙肾上腺素(isoprenaline hydrochloride,IPH)两种方法所建立的小鼠慢性心力衰竭(chronic heart failure,CHF)模型的差异及优缺点。方法:将24只6~8周雄性C57BL小鼠随机分为4组,即正常对照组(N组)、假手术组(A组)、药物模型组[腹腔注射15 mg/(kg.d)的IPH,B组]和手术模型组(主动脉弓缩窄术,C组),每组6只小鼠(n=6)。采用主动脉弓缩窄术和腹腔注射IPH建立小鼠CHF模型。分别于术后8周及连续腹腔注射IPH 11 d后8周,测量心脏质量/体质量比(HW/BW)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVEDS)、左室射血分数(LVEF)和短轴缩短率(FS)。使用PCR及琼脂糖凝胶电泳分析的方法检测心肌组织中心房钠尿肽(atrial natriuretic peptide,ANP)、脑尿钠肽(brain natriuretic peptide,BNP)、肌球蛋白重链(α-MHC)表达的水平,并行病理学检查。结果:主动脉弓缩窄术与腹腔注射IPH均成功地建立小鼠CHF模型。与N组比较,B组LVEDS增高36.06%,LVEF和FS分别降低24.88%和29.22%(P<0.01),单位面积下心肌细胞的数目减少24.80%(P<0.01)。与N组比较,C组的HW/BW明显升高(P<0.01),LVEDD和LVEDS分别增高27.42%和54.81%,LVEF、FS分别降低37.40%和42.17%(P<0.01),单位面积下心肌细胞的数目减少48.39%(P<0.01)。C组较B组HW/BW明显升高(P<0.01),单位面积下心肌细胞的数目减少更为显著(P<0.01)。结论:C组与B组相比,可以更良好地模拟后负荷增高导致的心力衰竭(HF),其病理生理过程与高血压导致的HF更接近,且与N组相比显著性较好,是理想的HF模型。 OBJECTIVE: To compare and evaluate the differences and advantages and disadvantages of the model of chronic heart failure (CHF) established by both aortic arch constriction and intraperitoneal injection of isoprenaline hydrochloride (IPH). Methods: Twenty-four male C57BL mice aged 6 to 8 weeks were randomly divided into 4 groups: normal control group (N group), sham operation group (A group) and drug model group (intraperitoneal injection of 15 mg / (kg.d) IPH, group B] and operation model group (aortic arch narrowing, group C), 6 mice in each group (n = 6). The mouse model of CHF was established by aortic arch narrowing and intraperitoneal injection of IPH. The cardiac mass / body mass ratio (HW / BW), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic diameter (LVEDS), left ventricular Ejection fraction (LVEF) and short axis shortening (FS). The atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and myosin heavy chain (α-MHC) expression were detected by PCR and agarose gel electrophoresis. The level of parallel pathology examination. Results: Aortic arch narrowing and intraperitoneal injection of IPH were successfully established mouse CHF model. Compared with group N, LVEDS increased 36.06%, LVEF and FS decreased 24.88% and 29.22% respectively in group B (P <0.01), and the number of cardiomyocytes in group B decreased by 24.80% (P <0.01). Compared with group N, HW / BW in group C were significantly increased (P <0.01), LVEDD and LVEDS were increased by 27.42% and 54.81% respectively, and LVEF and FS were decreased by 37.40% and 42.17% respectively (P <0.01) The number of cardiomyocytes decreased by 48.39% (P <0.01). The HW / BW in group C was significantly higher than that in group B (P <0.01), and the number of myocardial cells per unit area decreased more significantly (P <0.01). CONCLUSION: Compared with group B, group C can better simulate heart failure (HF) caused by increased post-load, and its pathophysiological process is more similar to HF caused by hypertension. Compared with group B, group C is significantly better than group N, Is the ideal HF model.
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