Blood flow restriction training improves the efficacy of routine intervention in patients with chronic ankle instability.

As a new means of rehabilitation, blood flow restriction training (BFRT) is widely used in the field of musculoskeletal rehabilitation. To observe whether BFRT can improve the efficacy of routine rehabilitation intervention in patients with chronic ankle instability (CAI). Twenty-three patients with CAI were randomly divided into a routine rehabilitation group (RR Group) and a routine rehabilitation â€‹+ â€‹blood flow restriction training group (RR â€‹+ â€‹BFRT Group) according to the Cumberland Ankle Instability Tool (CAIT) score. The RR Group was treated with routine rehabilitation means for intervention, and the RR â€‹+ â€‹BFRT Group was treated with a tourniquet to restrict lower limb blood flow for rehabilitation training based on routine training. Before and after the intervention, the CAIT score on the affected side, standing time on one leg with eyes closed, comprehensive scores of the Y-balance test, and surface electromyography data of tibialis anterior (TA) and peroneus longus (PL) were collected to evaluate the recovery of the subjects. Patients were followed up 1 year after the intervention. After 4 weeks of intervention, the RR â€‹+ â€‹BFRT Group CAIT score was significantly higher than the RR Group (19.33 VS 16.73, p â€‹< â€‹0.05), the time of standing on one leg with eyes closed and the comprehensive score of Y-balance were improved, but there was no statistical difference between groups (p â€‹> â€‹0.05). RR â€‹+ â€‹BFRT Group increased the muscle activation of the TA with maximum exertion of the ankle dorsal extensor (p â€‹< â€‹0.05) and had no significant change in the muscle activation of the PL with maximum exertion of the ankle valgus (p â€‹> â€‹0.05). There was no significant difference in the incidence of resprains within 1 year between the groups (36.36% VS 16.67%, p â€‹> â€‹0.05). The incidence of ankle pain in the RR â€‹+ â€‹BFRT Group was lower than that in the RR Group (63.64% VS 9.09%, p â€‹< â€‹0.01). Therefore, four-weeks BFRT improves the effect of the routine intervention, and BFRT-related interventions are recommended for CAI patients with severe ankle muscle mass impairment or severe pain.

[The antioxidant system mediated by Nrf2 in C2C12 cells responding to H2O2 stimulus under different oxygen concentration].

OBJECTIVE: To apply hypoxia of different oxygen concentration on C2C12 cells to study the changes of Nrf2 antioxidant system under H2O2. METHODS: The perfect simulative effect time and concentration of H2O2 were chosen. Cell vitality was tested after C2C12 cells cultured in 0.1 mmol/L, 0.25 mmol/L, 0.5 mmol/L, 0.75 mmol/L, 1 mmol/L and 2 mmol/L H2O2 for 1 or 2 h respectively. The C2C12 cells were divided into different oxygen concentration group: 21%O2, 12%O2, 8%O2, 5%O2 respectively. And then cells were treated with H2O2 for 1 h, and collected for determination. Immunofluorescence of Nrf2 and the protein expression of Nrf2 were detected. The expressions of antioxidant enzymes superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), catalase(CAT), NADPH quinine oxidoreductase-1 (NQO-1), glutathione peroxidase-1 (GPX-1), Heme oxygenase-1 (HO-1) mRNA and cellular ROS levels were tested by high quality fluorescence assay. RESULTS: 0.5 mmol/L H2O2 for 1 h was selected as the conditions of H2O2stimulation. Compared with 21% O2 group, the expressions of Nrf2 mRNA and protein, antioxidant enzymes SOD1, SOD2, CAT, HO-1, NQO-1, GPX-1 mRNA were increased significantly (P＜0.05 or P＜0.01), and ROS level was lower (P＜0.01) in 12%O2 group cells; only the expression of GPX-1 mRNA was increased (P＜0.05) in 8%O2 group; the expressions of Nrf2 mRNA and protein expression, antioxidant enzymes SOD1, SOD2, NQO-1, GPX-1 mRNA were decreased significantly(P＜0.05 or P＜0.01), and ROS level was higher (P＜0.01) in 5%O2 group. CONCLUSION: Hypoxia can affect the Nrf2 antioxidant system, and the different oxygen concentrations have different impact. In addition, 12% O2 for 12 h could promote the Nrf2 antioxidant system, and 5% extremely low oxygen may inhibit it.

Effects of acute hypoxia exposure with different durations on activation of Nrf2-ARE pathway in mouse skeletal muscle.

BACKGROUND: Hypoxia training enhances the endurance capacity of athletes. This response may in part be attributed to the hypoxia-induced increase in antioxidant capacity in skeletal muscles. Nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor which regulates the expression of genes via binding to the antioxidant-response element (ARE) of these genes, plays a crucial role in stimulating the body's defense system and potentially responds to hypoxia. Meanwhile, hypoxia-inducible factor-1α (HIF-1α) is an important player in protecting cells from hypoxic stress. The purpose of this study was to investigate the effects of acute hypoxia exposure with different durations on the activation of Nrf2-ARE pathway and a possible regulatory role of HIF-1α in these responses. METHODS: C57BL/6J mice were allocated into the non-hypoxia 0-hour, 6-hour, 24-hour, and 48-hour hypoxic exposure (11.2% oxygen) groups. The quadriceps femoris was collected immediately after hypoxia. Further, to investigate the possible role of HIF-1α, C2C12 myoblasts with HIF-1α knockdown by small interfering RNA (siRNA) and the inducible HIF-1α transgenic mice were employed. RESULTS: The results showed that 48-hour hypoxia exposure up-regulated protein expression of Nrf2, Nrf2/ARE binding activity and the transcription of antioxidative genes containing ARE (Sod1 and others) in mouse skeletal muscle. Moreover, HIF-1α siRNA group of C2C12 myoblasts showed a remarkable inhibition of Nrf2 protein expression and nuclear accumulation in hypoxia exposure for 72 hours compared with that in siRNA-Control group of the cells. In addition, HIF-1α transgenic mice gave higher Nrf2 protein expression, Nrf2/ARE binding activity and expressions of Nrf2-mediated antioxidative genes in their skeletal muscle, compared with those in the wild-type mice. CONCLUSIONS: The findings suggested that the acute hypoxia exposure could trigger the activation of Nrf2-ARE pathway, with longer duration associated with higher responses, and HIF-1α expression might be involved in promoting the Nrf2-mediated antioxidant responses in skeletal muscle.

Hypoxic Exercise Training Promotes apelin/APJ Expression in Skeletal Muscles of High Fat Diet-Induced Obese Mice.

Apelin, an endogenous ligand of the G-protein-coupled receptor APJ, is a novel myokine and may play a key role in regulating energy metabolism. The purpose of the present study was to investigate the effects of hypoxic exposure, exercise, and hypoxic exercise training on the expression of apelin and APJ in skeletal muscle of obese mice. Sixty two-months old C57BL/6J mice were randomly divided into two groups: Ten in normal diet group (N) and 50 in the high fat diet (HFD) groups. After two months of feeding, the HFD mice, whose body weight was 20% higher than the average weight of the N group, were selected as obese mice and further allocated into four groups: Control (C), Exercise (E), Hypoxia (H), and Exercise plus Hypoxia (E+H), at 8-9 mice/group. Besides body weight, measured variables in skeletal muscle were protein/mRNA levels of apelin/APJ, AMPKα-Thr172 phosphorylation, hypoxia inducible factor-1α (HIF-1α), mRNA levels of peroxisome proliferator-activated receptor α (PPARα), estrogen-related receptor (ERRα), and nuclear respiratory factor 1 (NRF1). Obese mice had significantly lower mRNA and protein expressions of apelin/ APJ in skeletal muscles than the normal body weight mice. After four weeks of interventions, hypoxic exercise training decreased body weight and increased mRNA and protein expressions of apelin and APJ, mRNA expression of ERRα, and protein expression of HIF-1α. These results indicate that changes of body weight may be associated with the levels of apelin/APJ expressions in skeletal muscle.