Changes of ACE and ERK in rabbits with hyperthyroid cardiomyopathy induced by Levothyroxine / 第三军医大学学报

ABSTRACT

Objective To explore the etiology of hyperthyroid cardiomyopathy. Methods Forty New Zealand rabbits were randomly and equally divided into 4 groups control group, levothyroxine(L-Thy) group, imidapril group, and valsartan group. Except the control group, rabbit model of hyperthyroidism was established by daily intraperitoneal injections of L-Thy (45 ?g?kg-1?d-1? 28 d), and the animals of later 2 groups received 0.5 mg/kg imidapril and 8 mg/kg valsartan respectively at same period. Ventricular tissues were collected at 4 weeks. Cardic hypertrophy index, cardiomyocyte diameter, structural and ultrastructural changes were detected. Cardiac fibrosis was displayed by Masson’s staining and collagen volume fraction (CVF) was measured using pathological image analytic system. Expressions of angiotensin converting enzyme (ACE), extracellular signal-regulated kinase (ERK), and phosphorylated ERK (p-ERK) were evaluated with Western blot analyses. Results Compared with control group, rabbits of L-Thy group displayed remarkable myocardial hypertrophy, extracellular matrix fibrosis, and morphological changes in both structure and ultrastructure. Western blot analysis revealed increased protein expressions of ACE,ERK and p-ERK proteins. ERK and p-ERK expressions were correlated positively well with both cardiomyocyte diameter and CVF. Both imidapril and valsartan alleviated cardiomyocyte hypertrophy, extracellular matrix fibrosis, and structural damage induced by L-Thy. Compared with L-Thy group, expressions of lower ERK and p-ERK were found in both imidapril and valsartan groups. Conclusion Renin-angiotension system (RAS) and ERK signaling pathway may play important roles in hyperthyroid cardiomyopathy. Activated RAS is possibly responsible for activation of ERK signaling pathway. Imidapril and valsartan may inhibit activation of ERK signaling pathway and retarding myocardial remodeling in hyperthyroid cardiomyopathy induced by L-Thy.