| Objective To study the protective effect of remote ischemic preconditioning (RIPC) of skeletal muscle on myocardial ischemia/reperfusion (I/R) injury in rabbit, and explore its possible mechanism.Methods To construct the model of remote ischemic preconditioning (RIPC) of skeletal muscle and myocardial ischemia/reperfusion (I/R) in rabbit. This study was divided into two parts. In the first part, it was divided into sham group, I/R group, and RIPC+I/R group (n= 6). In the second part, pre-treating rabbits with intraperitoneal injection of AMD3100 (CXCR4 inhibitor). It was divided into sham group, I/R group, AMD+I/R group, RIPC+I/R group, and AMD+RIPC+I/R group (n=6). And rabbit heart, peripheral blood and physiological ischemic skeletal muscle were accessed. TTC staining was applicated to detect myocardial infarct size, TUNEL staining was used to detect the apoptosis of myocardial cells, Western blot was used to detect the apoptosis and anti-apoptotic protein expression of myocardial tissue; ELISA to detect serum vascular endothelial growth factor (VEGF) and stromal cell derived factor-la (SDF-1α); Western blot and qRT-PCR was used to detect the expression of skeletal muscle hypoxia inducing factor (HIF-1α), SDF-1α and CXCR4 in myocardial tissue.Results The model of ischemic preconditioning (RIPC) of skeletal muscle and myocardial ischemia/reperfusion (I/R) in rabbit was successfully constructed. In the first part of the study, TTC staining and Tunel staining of rabbit heart showed that the myocardial infarct size and myocardial cell apoptosis rate of RIPC+I/R group were was lower than that of I/R group (P< 0.05). Western blot showed that the expression of apoptosis-related protein Bax of myocardial tissue in RIPC+I/R group was less than that of I/R_group (P< 0.05), while the expression of anti-apoptotic protein Bcl-2 in RIPC+I/R group was higher than that of I/R group (P< 0.05). In order to investigate the mechanism of RIPC to protect myocardial ischemia/reperfusion injury, The results of western blot and qRT-PCR showed that, the HIF-la, SDF-la expression of ischemic skeletal muscle in RIPC+I/R group was significantly higher than that of I/R group and sham group (P< 0.01). In addition, the CXCR4 expression of myocardial tissue with ischemia/reperfusion injury in I/R group and RIC+I/R group was significantly higher than that of sham group(P<0.01); The results of ELISA showed that, the VEGF, SDF-la levels in peripheral blood in RIPC+I/R group were higher than that of I/R group (P<0.01),RIPC+I/R group was significantly higher than that of I/R groupIn the second part of the study, pre-treating rabbits with intraperitoneal injection of AMD3100. The results of ELISA, Western blot and qRT-PCR showed that, compared to sham group, in I/R group, I/R+AMD group, RIPC+I/R group and AMD+RIPC+I/R group the SDF-1α levels in peripheral blood were significantly increased (P<0.05), while in RIPC+I/R and AMD+RIPC+I/R it increased much more (P<0.01), and there was no significant difference between I/R group and I/R+AMD group and between RIPC+I/R group and AMD+RIPC+I/R group. TTC staining and Tunel staining showed that the myocardial infarct size and myocardial apoptosis rate in RIPC+I/R group were less than that of I/R group, I/R+AMD group(.P < 0.05), and AMD+RIPC+I/R group (P< 0.05). The results of western blot showed that, the Bax expression of myocardial tissue in the RIPC+I/R group was lower than that of I/R group, I/R+AMD group (P< 0.05), and AMD+RIPC+I/R group (P<0.05); and the Bcl-2 expression in RIPC+I/R group was higher than that of I/R group, I/R+AMD group (P<0.05), and AMD+RIPC+I/R group (P< 0.05).Conclusion 1. Remote ischemic preconditioning (RIPC) of skeletal muscle had a protective effect on myocardial ischemia/reperfusion (I/R) injury;2. RIPC induced the expression of HIF-la in ischemic skeletal muscle and promoted the release of VEGF and SDF-1α into peripheral blood;3. RIPC promoted the expression of SDF-1α in ischemic skeletal muscle and I/R induced the expression of CXCR4 in myocardial tissue;4. AMD3100 inhibited the protective effect of RIPC on myocardial I/R injury, and the protection function of RIPC depended on the SDF-1α/CXCR4 passway.In conclusion, this study proved that RIPC induced the HIF-1α, SDF-1α mRNA expression of ischemic skeletal muscle, promoted SDF-la release into the peripheral blood and acting on Ectomesenchymal stem cell chemotaxis with CXCR4 to the myocardial cells, inhibited the myocardial infarction and apoptosis of myocardial cells, thus protected the myocardial ischemia/reperfusion injury.Objective The purposes of the study were to determine the effect of cuff ischemic training on vascular endothealial growth factor (VEGF) in patients with chronic total occlusion of coronary artery disease, to assess the effect of the training on myocardial ischemia and cardiac function, to provide the basis for patients with chronic total occlusion of coronary artery disease have cuff ischemic training.Methods 52 patients with chronic total occlusion of coronary artery disease were randomly assigned to either the training group (n=26) or control group (n=26), all patients were treated with conventional medical treatment, the patients in training group performed six-months training. Training was induced by cuff to block blood flow of limb, leading to temporary physiological ischemia of skeletal muscle. VEGF were determined by enzyme linked immunosorbent assay (ELISA), single-photon emission computed tomography (SPECT) was used to evaluate myocardial perfusion, ultrasonic cardiogram was used to evaluate left ventricular function,6 minutes walk test assess the overall activity function.Results VEGF levels increased significantly in training group from (83.51± 8.33) pl/ml to (118.60±9.07) p1/ml after six-months training (P<0.01), SPECT summed rest score (SRS) in training group from (13.18±1.45) score to (7.34±1.46) score after six-months training (P<0.01), there was no significant difference between 0 month and 6 month in control group (P>0.05). Left ventricular ejection fraction (LVEF) was no significant difference in two groups, Mitral valve early diastolic blood flow velocity (E)/Mitral valve early diastolic velocity (E,) reduce significant in training group (P<0.05),6 minutes walk distance increased significantly after six-months training (P<0.01), there was no significant difference between 0 month and 6 month in control group (P>0.05).Conclusions Cuff ischemic training could increase the level of VEGF in patients with chronic total occlusion of coronary artery disease. Cuff ischemic training may promote myocardial perfusion、left ventricular function and the overall activity function in patients with chronic total occlusion of coronary artery disease. |
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