关键词: 急性运动, 慢性运动, 干细胞移植, 骨髓间充质干细胞, 心肌梗死, 归巢

Abstract: BACKGROUND: Stem cell transplantation has a promising therapeutic prospect in the treatment of myocardial infarction, but the efficacy of stem cell transplantation is limited by the low homing efficiency of transplanted cells to the heart and the low retention rate and survival rate in the heart. Exercise therapy is an important integral component of cardiac rehabilitation for patients with myocardial infarction. However, the role of exercise in stem cell therapy for myocardial infarction has not yet been clarified. 
OBJECTIVE: To investigate the effect of exercise (including acute exercise and chronic exercise) on bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction.
METHODS: Eighty female SD rats were randomly divided into sham operation group, model group, transplantation group or combination group with random number table method (n=20). Myocardial infarction model of rats in model group, transplantation group, or combination group was made by coronary artery ligation. 24 hours after the model was made, the combination group underwent aerobic exercise for 8 weeks (chronic exercise, 30 min/d, 5 days per week), and within 5 minutes after the first exercise (acute exercise). SD rat bone marrow mesenchymal stem cells labeled with green fluorescent protein were injected into the tail vein of the transplantation group and the combination group. A part of animals from each group were taken 24 hours after the first exercise. The survival rate of stem cells transplanted into rat myocardium, sex-determining region of Y, protein expression of homing factors, oxidative stress, and inflammatory response parameters were measured. After 72 hours of the last exercise, the remaining rats were taken to detect cardiac structure and function, myocardial histological changes, and the number of Ki67+ cells.
RESULTS AND CONCLUSION: (1) After acute exercise: Compared with sham operation group, myocardial reactive oxygen species level, malondialdehyde content, tumor necrosis factor-α, and interleukin-1β protein expression increased (P < 0.05), and superoxide dismutase activity decreased (P < 0.05) in model group. Compared with model group, reactive oxygen species, malondialdehyde content, tumor necrosis factor-α, and interleukin-1β protein expression reduced (P < 0.05), superoxidation dismutase activity, stromal cell-derived factor 1α, and CXC chemokine receptor 4 protein expression increased (P < 0.05) in transplantation and combination groups. Compared with the transplantation group, reactive oxygen species, malondialdehyde content, tumor necrosis factor-α, and interleukin-1β protein expression decreased (P < 0.05), stem cell survival rate, sex-determining region of Y mRNA expression, superoxide dismutase activity, stromal cell-derived factor 1α, and CXC chemokine receptor 4 protein expression increased (P < 0.05) in combination group. (2) After chronic exercise: Compared with sham operation group, cardiomyocyte cross-sectional area and collagen content increased (P < 0.05), left ventricular ejection fraction and left ventricular short-axis shortening rate decreased (P < 0.05) in model group. Compared with model group, cardiomyocyte cross-sectional area and collagen content decreased (P < 0.05), Ki67+ cells increased (P < 0.05) in transplantation group. Compared with transplantation group, collagen content decreased (P < 0.05), cardiomyocyte cross-sectional area, left ventricular ejection fraction, left ventricular short-axis shortening rate, and Ki67+ cells increased (P < 0.05) in the combination group. (3) Acute exercise improves the survival rate of exogenous stem cells by promoting stem cell homing and improving myocardial microenvironment, while chronic exercise can stimulate cardiomyocyte proliferation, inhibit cardiac remodeling, and enhance cardiac function after stem cell transplantation. Therefore, exercise can help to optimize the efficacy of stem cell transplantation after myocardial infarction in rats.

Key words: acute exercise, chronic exercise, stem cell transplantation, bone marrow mesenchymal stem cell, myocardial infarction, homing