[Liraglutide improves cardiac structure and function in mice with advanced diabetic nephropathy and massive proteinuria].

OBJECTIVES: To investigate the effects of liraglutide on cardiac structure and function in a mouse model of diabetic nephropathy at the massive proteinuria stage. METHODS: Twenty 12-week-old male spontaneous type 2 diabetic KKAy mice were fed a high-fat diet for 10 weeks to establish diabetic models with massive proteinuria, which were then randomly divided into diabetic model group and liraglutide treatment group, with 10 age-matched C57BL/6J mice fed a standard chow diet serving as the normal control group. After 8 weeks of intervention, cardiac structural and functional parameters of the mice were evaluated using echocardiography, and myocardial histopathological changes were observed with HE staining, Masson's trichrome staining, Sirius red staining, and transmission electron microscopy. Serum levels of cardiac-related indicators were measured, and the mRNA and protein levels of collagen I and collagen III were determined using RT-qPCR and Western blotting, respectively. RESULTS: The diabetic mouse models showed significantly elevated blood glucose and increased body weight (<0.05) with disordered myocardial fibers, severe interstitial and perivascular fibrosis, and markedly upregulated myocardial expressions of collagen I and collagen III. Echocardiography revealed significantly increased left ventricular wall thickness, interventricular septal thickness, and left ventricular mass, reduced left ventricular internal diameter, decreased LVEF, FS, FAC, and the E/A ratio, and prolonged IVRT in the mouse models. Liraglutide treatment significantly improved these pathologies and alleviated cardiac functional impairment in the diabetic mice. CONCLUSIONS: Mice with diabetic nephropathy and massive proteinuria exhibit left ventricular hypertrophy and reduced cardiac function, accompanied by prominent myocardial interstitial fibrosis and inflammatory responses. Liraglutide improves cardiac structural and functional impairments in these mice possibly by alleviating myocardial fibrosis and inflammatory responses.