恩格列净灌胃对急性心肌梗死小鼠心功能的 改善作用及其机制.

Objective To investigate the protective effects of empagliflozin, a highly selective SGLT-2 inhibitor, on cardiac function in mice with acute myocardial infarction (AMI) and to explore its mechanism. Methods Thirty-four 6- week-old male C57BL/6J mice were randomly divided into the sham group (n=11), model group (n=11) and treatment group (n=12) . AMI was induced in the model group and treatment group by left anterior descending (LAD) artery ligation. The mice in the sham group underwent the same procedure except that the LAD was not ligated. The mice in the treatment group were given empagliflozin (10 mg/kg/day, oral gavage) at 4 h after MI surgery for 7 days. The mice in the sham group and model group were given 0. 5% hydroxyethyl cellulose. The left ventricular internal dimension in diastole (LVIDd), left ventricular internal dimension in systole (LVIDs), fractional shortening (FS) and ejection fraction (EF) were measured by echocardiography in all three groups. TUNEL staining was used to measure cardiac apoptosis. Blood samples were collected on day 7 after AMI to measure serum levels of NLRP3, ASC, Caspase-1, IL-1β, IL-18 and CRP by ELISA. The expression levels of NLRP3, ASC, Caspase-1, cleaved Caspase-1, IL-1β, and IL-18 were analyzed by Western blotting. Results There was no difference in LVIDd among these groups (P>0. 05). Compared with the sham group, the treatment group and model group had increased LVIDs (both P<0. 05). Compared with the sham group, the treatment group and the model group had decreased EF and FS, increased serum levels of NLRP3, IL-1β, IL-18, CRP, and up-regulated protein levels of NLRP3, ASC, cleaved Caspase-1, IL-1β, and IL-18 in the cardiac tissues of mice, with much more significant changes in the model group (all P<0. 05). The mice in the model group had significantly higher cardiac apoptosis rate than the sham group and the treatment group (both P<0. 05), while there was no statistical difference between the sham group and the treatment group (P>0. 05). There was no significant difference in the serum levels of Caspase-1 between the sham group and the model group (P>0. 05). Similarly, no statistical difference was found in the protein level of Caspase-1 in the cardiac tissues of mice among all three groups (P>0. 05). Conclusion Empagliflozin improves cardiac function and reduces cardiomyocyte apoptosis in AMI mice, and its mechanism may be related to the inhibition of the NLRP3/ASC/Caspase-1 signaling pathway and reduction of the inflammatory response. [ABSTRACT FROM AUTHOR]