Objective To explore the effect of liraglutide on cardiac function of mice with diabetes mellitus and concomitant myocardial infarction and its mechanism. Methods A total of 75 KM male mice were assigned to control group (15 mice) or model treatment group (60 mice) according to the random number table method. The diabetic mice model was established on 60 mice in the model treatment group, after successful modeling, the mice model of diabetes mellitus and concomitant myocardial infarction was established in 45 mice of the model treatment group selected by the random number table method; moreover, the remaining 15 mice were taken as sham operation group, and mice only underwent thoracotomy without coronary artery ligation. A total of 45 mice with diabetes mellitus and concomitant myocardial infarction were assigned to model group (n=15), myocardial infarction intervention group (n=15), or glucose intervention group (n=15) according to the random number table method, therein the myocardial infarction intervention group received intragastric administration of clopidogrel bisulfate+atorvastatin calcium tablets for intervention, the glucose intervention group was intervened by intraperitoneal injection of liraglutide injection, and the remaining mice did not receive any special treatment. After 7 days of intervention, electrocardiogram of mice in various groups was observed by using the electrocardiogram machine. The HE staining and 2, 3, 5-triphenyltetrazolium chloride staining were used to observe pathological status and myocardial infarction size of mice in various groups. The Western blot was used to detect protein expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and glycogen synthetase kinase 3β (GSK-3β) in myocardial tissues of mice in various groups. Results (1) There was no obvious abnormality in electrocardiogram of the control group and the sham operation group, and there was obvious ST-segment elevation and variant T wave in electrocardiogram of mice in the model group. ST-segment elevation and variant T wave of electrocardiogram in the myocardial infarction intervention group and the glucose intervention group were significantly improved, and the improvement effect of the myocardial infarction intervention group was superior to that of the glucose intervention group. (2) The myocardial fibers of mice in the control group and the sham operation group were arranged neatly and compactly, and the myocardial cells were intact; furthermore, compared with the control and sham operation groups, myocardial tissues of mice in the model group presented as infarct area, incomplete and disordered-arrangement myocardial cell morphology in the peri-infarct area, and a large number of inflammatory cell infiltration and fibrous tissue proliferation; in addition, compared with the model group, the aforementioned pathological changes were improved in the myocardial infarction intervention group and the glucose intervention group, and the improvement degree in the myocardial infarction intervention group was superior to that in the glucose intervention group. (3) Compared with the control group, there was no significant change in the percentage of size of myocardial infarction area in the sham operation group (P>0.05), and the percentage of size of myocardial infarction area in the model group was significantly increased than that in the control group and the sham operation group (P<0.05). Compared with the model group, the percentage of size of myocardial infarction area was reduced in the myocardial infarction intervention and glucose intervention groups (P<0.05), and the percentage of size of myocardial infarction area was smaller in the myocardial infarction intervention group than in the glucose intervention group, but no statistically significant difference was found (P>0.05). (4) Compared with the control group, the sham operation group exhibited elevated protein expressions of PI3K, AKT, and GSK-3β in myocardial tissues, whereas the model group yielded a decreased AKT protein expression in myocardial tissues, and an elevated GSK-3β protein expression in myocardial tissues (P<0.05), but there was no statistically significant difference in PI3K protein expression (P>0.05). Compared with the model group, the glucose intervention group interpreted elevated protein expressions of PI3K, AKT, and GSK-3β in myocardial tissues, whereas the myocardial infarction intervention group depicted elevated protein expressions of PI3K and AKT in myocardial tissues (P<0.05), but no statistically significant difference in GSK-3β protein expression was found (P>0.05). Compared with the myocardial infarction intervention group, the glucose intervention group implied elevated protein expressions of AKT and GSK-3β in myocardial tissues (P<0.05), whereas there was no statistically significant difference in PI3K protein expression (P>0.05). Conclusion Liraglutide can improve cardiac function injury, myocardial infarction size, and myocardial interstitial fibrosis in mice with diabetes mellitus and concomitant myocardial infarction, which may play a role by regulating expression of GSK-3β through PI3K/AKT signaling pathway.

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