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Objective: To investigate whether salidroside (Sal) protected the rat heart from exhaustive exercise-induced injury by inducing nuclear factor erythroid 2-related factor 2 (Nrf2) expression., Methods: Forty-eight male Sprague-Dawley rats were divided into four groups (n = 12 rats per group): the control, the exhaustive swimming (ES) group, the low-dose Sal plus acute exhaustive swimming (SLE) group, and the high-dose Sal plus acute exhaustive swimming (SHE) group. In the SLE and SHE groups, 15 and 30 mg/kg Sal were administered, respectively, once a day. The rats in the control and ES groups were administered the same amount of physiological saline, respectively, once a day. On the 14th day, the rats in the ES, SLE and SHE groups underwent exhaustive swimming training once. Then cardiac function parameters and electrocardiograms were recorded. Biomarkers of myocardial injury in the serum and oxidative stress factors in the myocardial tissue were evaluated using ELISA tests. The levels of Nrf2, nuclear Nrf2 and Kelch-like ECH-associated protein 1 (Keap1) messenger RNA and proteins were assessed in the myocardium using q-PCR and Western blotting, respectively., Results: Compared to the control group, the ES group showed remarkable increases in serum brain natriuretic peptide (BNP), cardiac troponin I (cTnI) and reactive oxygen species levels, but significant decreases in catalase and glutathione levels (p < 0.05). Compared to the ES group, the Sal treatment decreased serum BNP and cTnI levels and alleviated the changes in levels of oxidative stress-related factors. After treatment with Sal, nuclear and intracellular levels of Nrf2 protein were increased in the myocardial cells, while the level of Keap1 protein was decreased (p < 0.05)., Conclusions: Sal protected the heart from exhaustive exercise induced injury, and it may improve cardiac function and cardiac bioelectricity in exhausted rats by inducing Nrf2 expression.

Objective: To investigate the protection of salidroside of the heart against acute exhaustive injury and its mechanism of antioxidative stress and MAPKs signal transduction., Method: Adult male SD rats were divided into four groups randomly. Cardiomyocytes ultrastructure was observed by optical microscopy and transmission electron microscopy. The contents of CK, CK-MB, LDH, MDA, and SOD were determined by ELISA method, and the phosphorylation degrees of ERK and p38 MAPK were assayed by Western blotting. Cardiac function of isolated rat heart ischemia/reperfusion was detected by Langendorff technique., Results: Salidroside reduced the myocardium ultrastructure injury caused by exhaustive swimming, decreased the contents of CK, CK-MB, and LDH, improved the LVDP, ±LV dp/dt(max) under the basic condition, reduced the content of MDA and the phosphorylation degree of p38 MAPK, and increased the content of SOD and the phosphorylation degree of ERK in acute exhaustive rats., Conclusion: Salidroside has the protection of the heart against acute exhaustive injury. The cardioprotection is mainly mediated by antioxidative stress and MAPKs signal transduction through reducing the content of MDA, increasing the content of SOD, and increasing p-ERK and decreasing p-p38 protein expressions in rat myocardium, which might be the mechanisms of the cardioprotective effect of salidroside.

Brief exposure to tumor necrosis factor (TNF) is known to trigger subsequent cardioprotection. TNF activates multiple downstream signaling cascades including p38-MAPK, a kinase known to initiate ischemic preconditioning. However, it is not known whether this kinase is similarly involved in TNF-induced cardioprotection. In isolated perfused murine hearts, subjected to 30-min global ischemia/2-h reperfusion, infarction/risk volume was significantly reduced by pretreatment with TNF for 15 min at 0.5 ng/ml, but not at 5 or 10 ng/ml, followed by 10-min washout vs. control (% I/R = 31 +/- 3, 46 +/- 5 or 54 +/- 3 vs. 48 +/- 5; P = 0.01, 0.80 and 0.25, respectively). This was in direct contrast to the concentration dependence of myocardial p38-MAPK phosphorylation, as measured by dual phosphorylated p38-MAPK, which was apparent at TNF concentrations of 5 and 10 ng/ml but not at 0.5 ng/ml vs. time-matched control (as % basal 315 +/- 25, 422 +/- 94 and 97 +/- 25 vs. 95 +/- 10; P < 0.01, 0.01 and =0.86, respectively). However, phosphorylation of p38-MAPK at 10 min of ischemia was similar among groups (as % basal 393 +/- 98, 410 +/- 67 and 369 +/- 49 for time-matched control, 0.5 and 5 ng/ml, respectively). These patterns were also reflected in the phosphorylation of the downstream substrate HSP27. Furthermore, the effects of TNF on infarct size were not affected by SB203580 (1 micromol/l). These findings suggest that the pre-ischemic activation of p38-MAPK by TNF does not contribute to cardioprotection afforded by this agent.

Objective. To investigate whether exercise preconditioning (EP) improves the rat cardiac dysfunction induced by exhaustive exercise (EE) through regulating NOD-like receptor protein 3 (NLRP3) inflammatory pathways and to confirm which intensity of EP is better. Method. Ninety healthy male Sprague Dawley rats were randomly divided into five groups: a control group (CON), exhaustive exercise group (EE), low-, middle-, and high-intensity exercise precondition and exhaustive exercise group (LEP + EE, MEP + EE, HEP + EE group). We established the experimental model by referring to Bedford's motion load standard to complete the experiment. Then, the pathological changes of the myocardium were observed under a light microscope. Biomarker of myocardial injury in serum and oxidative stress factor in myocardial tissue were evaluated by ELISAs. The cardiac function parameters were detected using a Millar pressure and volume catheter. The levels of thioredoxin-interacting protein (TXNIP), thioredoxin protein (TRX), nuclear transcription factor kappa Bp65 (NF-ĸBp65), NLRP3, and cysteinaspartate specific proteinase 1 (Caspase-1) protein in rats' myocardium were detected by western blotting. Results. 1. The myocardial structures of three EP + EE groups were all improved compared with EE groups. 2. The levels of the creatine phosphating-enzyme MB (CK-MB), reactive oxygen species (ROS), interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor alpha (TNF-α) in three EP + EE groups were all increased compared with CON but decreased compared with the EE group (P < 0.05). 3. Compared with the CON group, slope of end-systolic pressure volume relationship (ESPVR), ejection fraction (EF), and peak rate of the increase in pressure (dP/dtmax) all dropped to the lowest level in the EE group (P < 0.05), while the values of cardiac output (CO), stroke volume (SV), end-systolic volume (Ves), end-diastolic volume (Ved), and relaxation time constant (Tau) increased in the EE group (P < 0.05). 4. Compared with the CON group, the expression levels of TXNIP, NF-ĸBp65, NLRP3, and Caspase-1 all increased obviously in the other groups (P < 0.05); meanwhile, they were all decreased in three EP + EE groups compared with the EE group (P < 0.05). 5. NLRP3 was positively correlated with heart rate, IL-6, and ROS, but negatively correlated with EF (P < 0.01). Conclusion. EP protects the heart from EE-induced injury through downregulating TXNIP/TRX/NF-ĸBp65/NLRP3 inflammatory signaling pathways. Moderate intensity EP has the best protective effect. [ABSTRACT FROM AUTHOR]

Objective. To investigate whether exercise preconditioning (EP) protects the rat heart from exhaustive exercise- (EE-) induced injury by inducing the PI3K-Akt signaling pathway. Methods. 84 male Sprague-Dawley rats were randomly divided into 6 groups (n = 14 rats per group): control group (Con), exhaustive exercise group (EE), exercise preconditioning group (EP), exercise preconditioning + exhaustive exercise group (EP + EE), LY294002 (PI3K inhibitor) + exercise preconditioning + exhaustive exercise group (LY + EP + EE), and LY294002 group (LY). The Con and LY did not exercise. The remaining groups were subjected to treadmill running. The structure of myocardial tissue and serum biomarkers of myocardial injury were observed. Hemodynamic parameters were recorded with a pressure-volume catheter. TUNEL assay was used to detect the apoptosis of cardiac myocytes, and the level of mitochondrial membrane permeability transforming pore (mPTP) in myocardium was evaluated using ELISA. Pathway and apoptosis-related proteins in myocardium were assessed using western blotting. Results. Compared to the Con group, the EE group showed remarkable myocardial injury, such as cardiac dysfunction and myocardial apoptosis. Compared to the EE group, the injuries in the EP + EE group were improved. EP increased the PI3K-Akt signaling pathway and regulated Bcl-2 family to decrease the mPTP openness level. However, the cardioprotective effects of EP were attenuated when pretreated with the LY294002. Conclusions. EP protected the heart from EE-induced injury, and it may improve the cardiac function and reduce the cardiomyocyte apoptosis by activating the PI3K-Akt signaling pathway. [ABSTRACT FROM AUTHOR]