Abstract: BACKGROUND: Stem cell therapy is an alternative treatment strategy for restoring damaged myocardial tissue after acute myocardial infarction. Exercise preconditioning can induce endogenous cardioprotective effects in the body. However, the efficacy and mechanism of the combined application are still unclear. 
OBJECTIVE: To explore the effect and possible mechanism of exercise preconditioning combined with bone marrow mesenchymal stem cells on the therapeutic effect in rats with acute myocardial infarction.
METHODS: Seventy male SD rats were randomly divided into sham operation group, model group, stem cell therapy group, exercise preconditioning group, and combined intervention group. Rats in the exercise preconditioning group and combined intervention group underwent 8-week aerobic exercise on the treadmill before modeling. The animal model of acute myocardial infarction was made by ligating the anterior descending coronary artery. The stem cell therapy group and the combined intervention group were injected with bone marrow mesenchymal stem cells (1×109 L-1, 1 mL) through the tail vein the next day after modeling. After 4 weeks of treatment, the exercise performance was evaluated by a graded treadmill exercise test. The cardiac structure and function were detected by echocardiography. The left ventricle was isolated. 2,3,5-Triphenyltetrazolium chloride staining was used to evaluate myocardial infarct size. Masson staining was used to obtain collagen volume fraction. CD31 immunohistochemical staining was used to detect myocardial capillary density. TUNEL staining was used to detect myocardial cell apoptosis. Immunoblotting was used to detect protein expression levels of stromal cell-derived factor 1, CXC chemokine receptor protein 4, tumor necrosis factor-α, interleukin-10, and vascular endothelial growth factor. 
RESULTS AND CONCLUSION:  (1) Intervention efficacy: Compared with the sham operation group, exercise performance, left ventricular ejection fraction, left ventricular fractional shortening, and CD31 positive cell rate decreased (P < 0.05); myocardial infarct size, collagen volume fraction, and myocardial apoptotic rate increased (P < 0.05) in the model group. Compared with the model group, exercise performance was not statistically significant (P > 0.05) in the stem cell therapy group, and the exercise performance improved (P < 0.05) in the exercise preconditioning and combined intervention groups; left ventricular ejection fraction, left ventricular fractional shortening, and CD31 positive cell rate increased (P < 0.05), and the myocardial infarct size, collagen volume fraction, and cardiomyocyte apoptosis rate decreased (P < 0.05) in the stem cell therapy, exercise preconditioning, and combined intervention groups. Compared with the stem cell therapy group, exercise performance, left ventricular ejection fraction, left ventricular shortening fraction, and CD31 positive cell rate increased (P < 0.05), myocardial infarct size, collagen volume fraction, and myocardial cell apoptosis rate decreased (P < 0.05) in the combined intervention group. (2) Protein expression: Compared with the sham operation group, the expression of tumor necrosis factor-α increased (P < 0.05), while interleukin-10 and vascular endothelial growth factor expression decreased (P < 0.05) in the model group. Compared with the model group, the expression of CXC chemokine receptor protein 4 increased (P < 0.05) in the stem cell therapy group and combined intervention group, and the expression of tumor necrosis factor-α decreased (P < 0.05) while interleukin-10 and vascular endothelial growth factor increased (P < 0.05) in the stem cell therapy group, exercise preconditioning group, and combined intervention group. Compared with the stem cell therapy group, the expression of tumor necrosis factor-α decreased (P < 0.05), while CXC chemokine receptor protein 4, interleukin-10, and vascular endothelial growth factor increased (P < 0.05) in the combined intervention group. To conclude, exercise preconditioning can enhance the therapeutic effect of bone marrow mesenchymal stem cells in rats with acute myocardial infarction, which can inhibit cardiac remodeling, improve cardiac function, and delay the progress of heart failure. Its mechanism is related to the promotion of stem cell homing, inhibition of inflammatory response, and promotion of angiogenesis.

Key words: exercise preconditioning, acute myocardial infarction, bone marrow mesenchymal stem cell, homing, cardiac remodeling