RESUMO
PURPOSE: Increased evidence has shown that aerobic exercise reduces airway hyperresponsiveness in asthmatic individuals. However, the underlying mechanisms of action remain elusive. This study aimed to investigate the effect of exercise on airway smooth muscle (ASM) contractile function in asthmatic rats, and uncover the possible involvement of interleukin 4 (IL-4) and the store-operated Ca2+ entry (SOCE) pathway. METHODS: In this study, chicken ovalbumin was used to induce asthma in male Sprague-Dawley rats. The exercise group received moderate-intensity aerobic exercise training for 4 weeks. IL-4 concentrations in bronchoalveolar lavage fluid (BALF) samples were evaluated by enzyme linked immunosorbent assay. The contractile function of the ASM was investigated using tracheal ring tension experiments and intracellular Ca2+ imaging techniques. Western blot analysis was used to evaluate expression levels of calcium-release activated calcium (CRAC) channel protein (Orai) and stromal interaction molecule 1 (STIM1) in ASM. RESULTS: Our data showed that the carbachol-stimulated, SOCE-mediated contraction of rat ASM was significantly increased in asthmatic rats, which could be abolished by exercise. Pharmacological studies revealed that GSK5498A and BTP-2, selective blockers of CRAC channels significantly inhibited SOCE-induced ASM contraction. In addition, exercise inhibited the up-regulation of IL-4 in BALF as well as STIM1 and Orai expression in the ASM of asthmatic rats. In line with these observations, we demonstrated that pretreatment of the ASM with IL-4 up-regulated the expression level of STIM1, Orai1 and Orai2, thereby promoting SOCE-mediated ASM contraction. CONCLUSIONS: The data in this study reveal that aerobic exercise may improve the ASM contractile function in asthmatic rats by inhibiting IL-4 secretion and by down-regulating the expression of STIM1, Orai1 and Orai2, thus decreasing excessive SOCE-mediated ASM contraction in asthmatic rats.
RESUMO
A new multi-point inflow pre-anoxic/oxic/anaerobic/anoxic/oxic (A1/O2/A3/A4/O5) sludge-membrane coupling process and pilot plant were developed and designed to solve the problem of nitrogen and phosphorus removal of low carbon and nitrogen (C/N) ratio domestic sewage in southern China. The removal effect and transformation rule of organic matter, nitrogen, and phosphorus in the system were studied by changing the distribution ratio of multi-point influent. The average C/N ratio of the influent was 2.09 and the influent distribution ratio was 1:1. When the temperature was 16-25 °C, the average concentrations of chemical oxygen demand (COD), ammonia nitrogen (NH4+- N), total nitrogen (TN), and total phosphorus (TP) in the effluent were 21.31 (±2.65), 0.60 (±0.24), 12.76 (±1.09), and 0.34 (±0.05) mg/L, respectively, and their average removals are 87.3 (±1.2)%, 98.7 (±0.4)%, 74.1 (±1.3)%, and 88.1 (±0.4)% respectively. When the low temperature was 12-15 °C, the average removals were 78.6 (±1.1)%, 90.5 (±1.3)%, 73.7 (±1.13)%, and 86.6 (±1.7)%, respectively. Compared with the traditional anaerobic/anoxic/aerobic (A2O) process under the same conditions, the TN removal was increased by 15.4%, and the TP removal was increased by 22.2%. This system has obvious advantages in treating wastewater with low C/N ratio, thereby solving the problem wherein the effluent of biological phosphorus removal from low C/N ratio domestic sewage was difficult when it was lower than 0.5 mg/L.
