Background:when acute occlusion of coronary artery leads to myocardial infarction, the main strategy is to open the occluded vessels as soon as possible and restore the blood supply of myocardial cells in order to improve the early survival rate. However, the left ventricular remodeling after acute myocardial infarction will lead to progressive decline of left ventricular systolic function and heart failure, and the consequences are serious. Experimental studies have shown that the location of myocardial infarction and the supply vessels related to infarction are related to left ventricular remodeling, among which the occlusion of the anterior wall myocardial infarction and the anterior descending branch supply vessels is related to the reconstruction of left ventricular after acute myocardial infarction.
Sodium glucose co transporter-2 inhibitors (SGLT-2i) were used as a novel hypoglycemic drug not acting on pancreatic cells in the early stage. The drug can inhibit the reabsorption of glucose by sodium glucose cotransporter 2 distributed in the proximal tubules of kidney, thus increasing the excretion of glucose through urine and achieving the effect of reducing blood glucose.
Although a large number of studies have proved that SGLT-2 inhibitors can improve cardiac function, SGLT-2 is not expressed in the heart, so its effect on improving cardiac function may not depend on inhibiting sodium glucose transport. Therefore, the mechanism of SGLT-2 inhibitors to improve cardiac function is worth further exploring.
The protective mechanism of SGLT-2 inhibitors on damaged cardiomyocytes has not been elucidated, and whether SGLT-2 inhibitors have protective effects on ventricular remodeling after acute myocardial infarction remains unclear. Whether SGLT-2 inhibitors can inhibit excessive apoptosis of cardiomyocytes and improve myocardial fibrosis by inhibiting the secretion of inflammatory mediators and chemokines by inflammatory cells, so as to reduce ventricular remodeling and preserve and improve cardiac function as a whole.
Objective: (1) to establish an animal model of acute myocardial infarction (AMI) in the anterior wall of mice by ligating the left anterior descending artery (LAD) with ophthalmic sutures after identifying the coronary artery in mice. (2) Objective To observe whether SGLT-2 inhibitor can improve left ventricular remodeling caused by myocardial oxidative stress, myocardial fibrosis and apoptosis after acute myocardial infarction.
In this experiment, 54C57B/L6 male mice were selected and divided into three groups according to the random principle. Each group of 14 mice were divided into three groups: the anterior descending coronary artery was ligated and the acute myocardial infarction group was established, The rats without ligation were treated withDagliflozin(AMI + DAPA group, the dose was 30mg/ (kg·d));the mice without ligation were treated as sham operation group (sham group). The same dose of 0.9% sodium chloride injection was given to AMI group and sham group.
In this experiment, the blood was collected from the canthus on the 7th day of AMI model in mice, and the concentrations of malondialdehyde, SOD and hs-CRP were measured in the serum of each group of mice. The influence of dagglinet intervention on the inflammatory index was evaluated by group comparison analysis, and the results were concluded Inhibition of the reaction. The changes of cardiac function and structure were monitored by echocardiography on the 3rd, 7th and 14th days of each group. The NT-proBNP value was detected.
The operation distinguished the coronary artery of mice. After ligation of Qianjiang sub branch, the local white and cyanosis of the anterior wall of the ventricles was observed in a short time after ligation. The ST segment elevation was obvious in ECG, which suggested that the modeling was successful. The concentrations of hs-CRP, TNF-and MDA in the plasma of the mice were significantly higher on the third and seventh days after the establishment of AMI model, and there was significant difference compared with the sham operation group (P <0.05);the prognosis of the group with Dagliflozindry decreased, and the difference was significant (P <0.05);at the same time, the sod concentration was significantly decreased, and there was significant difference with sham operation group (P <0.05);and Dagliflozinintervention was given The results showed that Dagliflozincould inhibit the acute inflammation caused by AMI to some extent.
The cardiac function of the group with dapglinet was higher than that of the acute myocardial infarction group on the 7th and 14th days after the induction of myocardial infarction in mice. Meanwhile, NT-proBNP, the marker of cardiac function, was monitored, while that of the treatment group was significantly reduced (P <0.05).
1. After the intervention of dapagliflozin, it can improve left ventricular remodeling after acute myocardial infarction in mice, and has a certain protective effect on heart function.
2. After the intervention of dapagliflozin on the mouse model of acute myocardial infarction, it has the effect of inhibiting the levels of serum TNF-and hs-CRP in mice and inhibiting the inflammatory response in the acute phase of myocardial infarction. Its effect of inhibiting ventricular remodeling may be mainly related to reducing the concentration of TNF-.
3. After the intervention of dapagliflozin, lipid peroxidation was inhibited and MDA level decreased;at the same time, antioxidant enzyme level was increased, SOD level increased, which played a role in inhibiting oxidative stress.
4. It can be inferred that dapagliflozin may promote the transformation of macrophages from M1 to M2 by inhibiting the expression of TNF-, and strengthen the transformation of macrophages to "amoebic"morphology, thereby enhancing the myocardium. Protective effect, interfere with the occurrence and development of early ventricular remodeling.
5. It can also be speculated that dapagliflozin may improve the energy supply of cardiomyocytes by restoring the phosphorylation pathway, improve cardiomyocyte apoptosis, and further protect the heart.
Keywords:Dagliflozin;Acute Myocardial Infarction;Oxidative Stress;Inflammatory Response;Left Ventricular Remodeling.|