Abstract:Aim To study the effect of liraglutide on myocardial metabolites and related metabolic pathways in diabetic cardiomyopathy (DCM) rats. Methods Among 60 SPF male SD rats aged 3 weeks, 10 rats were randomly selected as normal control group (n＝10), and the remaining 50 rats were established by peritoneal injection of streptozotocin combined with high-sugar and high-fat diet for DCM rat model. A total of 36 rats were successfully modeled for DCM and randomly divided into DCM model group (DCM group, n＝12), low-dose liraglutide treatment group (LL group, n＝12) and high-dose liraglutide treatment group (HL group, n＝12). Rats in LL group (100 μg/kg) and HL group (200 μg/kg) were given intraperitoneal injection of liraglutide once a day. And after 12 weeks of intervention, the rats were killed under anesthesia after echocardiography to detect cardiac function, and the heart tissues were taken for metabolomics detection. The differential metabolites and related pathways that may be related to liraglutide improving myocardial metabolism in DCM rats were screened and enriched. Results Compared with normal control group, left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in DCM group were significantly decreased, and the ratio of early to late diastolic mitralflow velocities (E/A) was significantly increased (P＜0.05). Compared with DCM group, LVEF and LVFS in LL group and HL group were significantly increased, and E/A ratio was significantly decreased (P＜0.05), suggesting that the impairment of left ventricular systolic and diastolic function in LL group and HL group was significantly alleviated. 395 metabolites were detected by metabolomics, among which 9,6 and 187 different metabolites and 3,6 and 20 metabolic pathways were enriched in DCM group and normal control group, LL group and DCM group, HL group and DCM group. In the above three groups, 29 key differential metabolites were identified related to 3 metabolic pathways including choline metabolic pathway, caffeine metabolic pathway and valine, leucine and isoleucine biosynthesis pathway, among which choline metabolic pathway had the most significant differences. Conclusion These results indicated that liraglutide can ameliorate cardiac dysfunction in DCM rats through improving myocardial metabolism in which choline metabolism pathway may play a key role.
