Effects of chronic intermittent hypoxia on atrial structural remodeling in rats

Abstract

Objective The rat model of chronic intermittent hypoxia(CIH) was established to investigate the effects of CIH on atrial structural remodeling and signaling pathway related fibrosis in rats. Methods Fifteen Sprague-Dawley male rats were divided into control group(4 rats), CIH group(6 rats)and CIH+ enalapril(EN) group(5 rats). Five hours intermittent hypoxia per day for 3 weeks was conducted in CIH group and CIH+ EN group. EN group was given enalapril 10 mg·kg-1·d-1 intragastrically before hypoxia and same amount of saline in CIH and control group. All three groups were normally feeding. All the left and right atrial tissue from all rats were harvested after 3 weeks. The histologic changes of atrial tissue was observed by HE staining. The features of atrial fibrosis, collagen volume fraction(CVF), were evaluated by Masson staining. And the protein expression levels of ERK1/2, p-ERK1/2 and NF-κB were determined by immunohistochemical staining. Results Heterogeneity in the size and arrangement of atrial myocytes was observed and myocardial tissue space was increased in the CIH group, enalapril treatment could ameliorate the changes. The degree of atrial fibrosis(CVF)in CIH group was significantly higher than that in control group(P <0.05), while enalapril could alleviate the degree of fibrosis(P <0.05). The protein expression of ERK1/2, p-ERK1/2 and NF-κB was significantly elevated in CIH group compared with that in control group(P <0.05), enalapril inhibited the expression of ERK1/2, p-ERK1/2(P <0.05). Conclusion CIH could cause atrial fibrosis and structural remodeling, ERK and NF-κB signaling transduction pathway may participate in the regulation of atrial structural remodeling, RAAS inhibitors could alleviate atrial remodeling through inhibiting ERK signal transduction pathway. Key words: Chronic intermittent hypoxia; Atrial structural remodeling; Fibrosis; extracellular signal regulated kinase