[Animal modeling] - Improvement and evaluation of conditions of rat model of myocardial hypertrophy induced by isoproterenol based on implantable osmotic pump

  Objective Myocardial hypertrophy is a slowly developing and effective compensatory function, an adaptive response to hemodynamics or myocardial injury, and an independent risk factor leading to heart failure. It has been reported that the rat model of myocardial hypertrophy induced by isoproterenol (ISO) has a large difference in administration route and induction dose, and the development process of pathological phenotype of the model animal is uneven.

  Methods based on the progressiveness of the previous methods, the homogeneity of the model phenotype, the stability of the methods and the difficulty of replication, a rat model of myocardial hypertrophy was induced by low-dose long-term administration of ISO (4 mg / kg, lasting for 28 days) by subcutaneous implantation of osmotic pump, and the phenotype of the model was evaluated by ultrasound image, histopathological staining, immunofluorescence staining and real-time PCR.

  Results The pathological phenotype of model rats was typical. Overall phenotype, including increased cardiac volume, ventricular wall thickness and cardiac weight index; Cell phenotype, including enlarged myocardial cells, severe myocardial fibrosis, rupture and dissolution of myocardial fibers, disappearance and vacuolization of mitochondrial ridges, distortion and blurring of myocardial Z lines, M lines and intercalated discs; Molecular phenotypes, including cardiac natriuretic peptide (ANP), a marker of cardiac hypertrophy, and brain natriuretic peptide (BNP), were significantly increased.

  Conclusion The rat model of myocardial hypertrophy established in this paper is stable and reproducible, with typical phenotypic characteristics, and is more suitable for scientific research such as gene function analysis and related drug screening.