关键词: 心脏疾病, 纤维化, 异丙肾上腺素, NF-&kappa, B

Abstract: Objective：To establish a model of cardiac fibrosis induced by isoproterenol (ISO), the non-selective β adrenoceptor agonist, injected subcutaneously for 7 days in rats, and to observe changes of transcription factor NF-κB in the model.Methods: Male SD rats weighing 280-320 g were injected with ISO ［0.25 mg/(kg·d)］ subcutaneously for 7 days to induce cardiac fibrosis. The collagen volume fraction was determined by quantitative morphometry of picrosirius red stained left ventricular sections. Collagen types Ⅰ/Ⅲ and IL-6 mRNA expressions were analyzed by real time PCR. The pathological changes of the heart were investigated by Hematoxylin and Eosin staining. NF-κB was localized by immunohistochemistry (IHC) and phosphorylated NF-κB levels were assessed by Western blot analysis.Results: Compared with the controls, ISO significantly elevated the sirius red stained area and collagen volume fraction (12.01±1.644 vs. 0.95±0.067, P＜0.001). Similarly, ISO increased the mRNA expressions of collagen Ⅰand collagen Ⅲ of the heart compared with the controls (10.51±0.47 vs. 0.98±0.02，P＜0.001 for collagen I; 9.58±1.33 vs. 1.02±0.02, P＜0.001 for collagen Ⅲ). The number of nuclei was increased and nuclear accumulation was presented in myocardial tissue induced by ISO. The mRNA expression of IL-6 increased in ISO group (1.64±0.18 vs. 1.04±0.07, P<0.01). ISO induced NF-κB nuclear translocation, accompanied by an increase in phosphorylation of NF-κB  (10.83±2.05 vs. 1.05±0.27, P＜0.001).Conclusion: We conclude that the model of cardiac fibrosis can be successfully induced by ISO injected subcutaneously for 7 days in rats and the activation of nuclear factor NF- κB increased by β-adrenoceptor stimulation.

Key words: Cardiomyopathies, Fibrosis, Isoproterenol, NF-kappaB