| Objetives:The aim of this study was to investigate the effects of interval exercise training on the expression of LIF and LIFR as well as the MI-induced skeletal muscle atrophy and cardiac function.Methods:Adult male sprague-dawley rats,3-mouth old, were randomly divided into five groups:Sedentary control group (Control), interval exercise group (CE), Sham-operated group (Sham), sedentary MI group (MI) and MI with interval exercise group (ME). The MI model was established by ligation of the left anterior descending(LAD) coronary artery, and rats in CE and ME were subjected to 8 weeks interval training. Cardiac function, heart tissue remodeling, cardiomyocyte and gastrocnemius cell apoptosis were evaluated after the training. The expression of LIF, LIFR, p-STAT3, STAT3, Bcl-2, Bax, VEGFA and a-SMA was determined in the peri-infarcted area of the left ventricle and gastrocnemius by Western Blotting or RT-qPCR. The protein expression levels of LIF, LIFR, vWF and CD31 were detected by immunofluorescence or immunohistochemical measurement.Results:(1) Interval exercise training prevents myocardial infarction induced skeletal muscle atrophy in rats. The MI rats showed a significant decrease muscle mass and the ratio of gastrocnemius muscle/tibia length and CSA and a-actin and ?-myosin protein expression in the gastrocnemius compared with the sham group. In contrast, the ME group subjected to interval training showed the muscle mass and the ratio of gastrocnemius muscle/tibia length and CSA and a-actin and a-myosin protein expression in the gastrocnemius was significantly increased compared with MI groups, suggesting that interval training prevented muscle atrophy in MI rats.(2) Effect of interval training on LIF/LIFR signal transduction by STAT3 in gastrocnemius muscle in normal and myocardial infarction rats. The gene and protein levels of LIF/LIFR and p-STAT3 were higher in CE group compared with the Control group. The gene and protein levels of LIF/LIFR and p-STAT3 were higher in ME group compared with the MI group. Together, these data suggest that MI significantly reduced LIF expression and impaired its signal transduction. However, this down regulation of LIF expression and signal transduction could be prevented by interval.(3) Interval exercise training activates LIF-LIFR-STAT3 in gastrocnemius muscle in myocardial infarction rats.The gene and protein levels of LIF/LIFR and p-STAT3 were higher in ME group compared with the MI group. Together, these data suggest that MI significantly reduced LIF expression and impaired its signal transduction. Interval exercise training activates LIF-LIFR-STAT3 signaling pathway in the gastrocnemius.(4) Effect of MI and interval training on cell apoptosis in gastrocnemius muscle. The results showed that TUNEL positive particles and Bax were increased markedly, the anti-apoptotic protein Bcl-2 level and Bcl-2/Bax ratio was decreased in the MI group compared with the Sham group. In contrast, TUNEL positive particles and Bax expression were decreased markedly, Bcl-2 expression and Bcl-2/Bax ratio was elevated in the ME group compared with the MI group. Collectively, these data indicate that MI increase apoptosis in gastrocnemius muscle, and this can be blocked by interval training.(5) Interval training on activates LIF/LIFR/STAT3 pathway in myocardial of normal. Compared with the sham group, the gene protein levels of LIF/LIFR and p-STAT3 were lower in the MI group. In contrast, the gene and protein levels of LIF/LIFR and p-STAT3 were higher in ME group compared with the MI group. Together, these data suggest that MI significantly reduced LIF expression and impaired its signal transduction. However, this down regulation of LIF expression and signal transduction could be prevented by interval exercise training.(6) Interval exercise training prevents myocardial apoptosis in rats with myocardial infarction.The results showed that TUNEL positive particles and Bax protein expression were increased and Bcl-2 protein expression were lower markedly in the MI group compared with the Sham group. In contrast, TUNEL positive particles and Bax were decreased and Bcl-2 protein expression were increased markedly in the ME group compared with the MI group. However, the myocardial apoptosis could be prevented by interval exercise training.(7) Interval exercise training prevents angiogenesis in rats with myocardial infarction. Compared with the sham group, the infarction fringes microvascular density and VEGF-A protein expression decreased significantly, new blood vessels density and a-SMA protein expression increased significantly. In contrast, the VEGF-A protein expression, the infarction fringes microvascular density and new blood vessels density increased significantly, the protein expression of a-SMA was reduced significantly in the ME group. Collectively, these data indicated that interval exercise training increases angiogenesis in rats with myocardial infarction(8) Interval exercise training increases LIF expression in serum in rats with myocardial infarction and normal. LIF can secrete LIF target organs into the blood stream while the body by external stimuli.(9) Interval exercise training decreases significantly CVF%, increases Cardiac remodeling and cardiac function in rats with myocardial infarction.(10) LIF expression in Skeletal muscle was correlated with the apoptosis of skeletal muscle cells; LIF expression in heart was correlated with the level of cardiomyocytes apoptosis, angiogenesis and heart function improvement; LIF protein expression in skeletal muscle, serum and heart were significantly associated with the parameters of cardiac function. Presumably, Interval exercise training inhibited skeletal muscle atrophy, stimulated skeletal muscle to secret LIF into the blood, and LIF bounded with LIFR in heart and then activated LIF-LIFR-STAT3 pathway, consequently, cardiomyocytes apoptosis was inhibited, myocardium vascular regeneration was improved, microcirculation and pathological cardiac remodeling, heart function would be improved by interval exercise training after myocardial infarction.Conclusion:1. Interval exercise training significantly improves skeletal muscle atrophy in rats with myocardial infarction; activates LIF-LIFR-STAT3 signaling pathway in skeletal muscle of normal and myocardial infarction rats, and inhibites apoptosis of skeletal muscle cells in rats with myocardial infarction.2. Interval exercise training activates LIF-LIFR-STAT3 signaling pathway in normal and infarcted rat, and inhibites cardiomyocyte apoptosis, promotes the regeneration of blood vessels in the MI edge district, reduces CFS in MI rats, so that improved MI heart pathological remodeling, significantly improved cardiac function in rats with myocardial infarction.3. Interval exercise training significantly increases the expression level of serum LIF in the normal and MI rats. Expression of LIF in skeletal muscle had deeply associated with with the apoptosis of skeletal muscle cells. LIF expression in heart was correlated with the level of cardiomyocytes apoptosis, angiogenesis and heart function improvement. LIF protein expression in skeletal muscle, serum and heart were significantly associated with the parameters of cardiac function4. The underlying mechanism of the effect that Interval exercise training inhibites skeletal muscle atrophy and improves heart function after myocardial infarction is that interval exercise training stimulated skeletal muscle to secret LIF into the blood, and LIF bounded with LIFR in heart and then activated LIF-LIFR-STAT3 pathway. Consequently, cardiomyocytes apoptosis was inhibited, myocardium vascular regeneration was improved, microcirculation and pathological cardiac remodeling, heart function would be improved by Interval exercise training after myocardial infarction. |
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