|
Effects of dapagliflozin on cardiac function and myocardial remodeling in rabbits with non-diabetic chronic heart failure
CHEN Xuefeng, ZHAO Ming, ZHANG Yu, HAO Ziqiang, BAI Wenlou, MENG Cunliang, QI Xiaoyong
2022, 50 (7):
719-725.
doi: 10.11958/20220040
Objective To investigate the effects of dapagliflozin on cardiac function and myocardial remodeling in rabbits with non-diabetic chronic heart failure. Methods A total of 18 male New Zealand white rabbits were randomly divided into the sham group, the heart failure group and the dapagliflozin group, with 6 rabbits in each group. The sham group only performed thoracotomy without operation, and the heart failure group and the dapagliflozin group were treated with aortic constriction after thoracotomy. Nondiabetic chronic heart failure model was established after 12 weeks. The general situation was observed in each group. The dapagliflozin group was given dapagliflozin 1 mg/ (kg·d) by force-feeding method 13 weeks after operation, and the sham group and the heart failure group were given the same amount of normal saline for a total of 10 weeks. Echocardiography was performed before surgery, 12 weeks after surgery and 10 weeks after drug intervention. Body weight, white blood cell (WBC) count, total protein, albumin, hemoglobin, potassium, sodium, random blood glucose, osmotic pressure and NT-proBNP were detected after 10 weeks of drug intervention. After the animals were sacrificed, whole heart and left ventricle mass were measured, the morphology and fibrosis degree of myocardial tissue were observed by HE, Masson and immunohistochemistry staining, and collagen tissue fraction and positive percentage of Collagen Ⅰ or Ⅲ area were calculated. Results Dapagliflozin ameliorated symptoms such as loss of appetite, lethargy, reduced activity and tachypnea in animals with heart failure. After 10 weeks of drug intervention, the left ventricular ejection fraction (LVEF) was significantly higher in the dapagliflozin group than that in the heart failure group, and significantly higher than that of 12 weeks after operation (P<0.05). There were no significant differences in levels of WBC, hemoglobin, total protein, albumin, potassium, sodium, blood glucose and osmotic pressure between the three groups. The hemoglobin concentration were lower in the dapagliflozin group and the heart failure group compared with that of the sham group, but there was no significant difference between the dapagliflozin group and the heart failure group. Compared with the heart failure group, the heart shape of dapagliflozin group was decreased, and the total heart mass, left ventricular mass and left ventricular/body mass of the dapagliflozin group were lower than those of the heart failure group (P<0.05). HE staining showed that dapagliflozin could significantly improve the morphological changes of myocardial cells. Masson staining showed that collagen fiber fraction in myocardial tissue was significantly reduced in the dapagliflozin group compared with that of the heart failure group (P<0.05). Immunohistochemical analysis showed that the percentage of positive Collagen Ⅰ and Collagen Ⅲ area in myocardial tissue of the dapagliflozin group was lower than that of the heart failure group (P<0.05). Conclusion Dapagliflozin inhibits cardiac remodeling after heart failure, the mechanism of which may be related to the inhibition of Collagen Ⅰ and Ⅲ expression in myocardial tissue and myocardial fibrosis.
Related Articles |
Metrics
|