Exercise Training in Hypoxia Prevent Hypoxia Induced NLRP3 Inflammasome Activation in Skeletal Muscles / 中国运动医学杂志

ABSTRACT

Objective To observe the effect of exercise training in hypoxia on the activation of NL-RP3 inflammasomes in skeletal muscles,and to explore the role of nuclear factor(erythroid-derived 2)-like 2 (Nrf2).Methods Thirty-two male Sprague-Dawley rats were randomly divided into a normoxia control (NC) group,a normoxia training (NT) group,a hypoxia control (HC) group and a hypoxia training (HT) group,each of 8.The hypoxia animals were housed in normobaric hypoxic tent with oxygen content of 11.3％ for 4 weeks consecutively.The animals exercised on a motor-driven rodent treadmill of a 5％ slope at a speed of 15 m/min for 60 min/day,5 days/week.Following the last hypoxia exposure,all rats were sacrificed by decapitation and their quadriceps were removed.Their muscle mitochondria were extracted using the differential velocity centrifugation.The generation of mitochondrial reactive oxygen species(ROS)was detected using the dichlorofluorescein method.The 8-oxodG in the mitochondral DNA was measured using the high-performance liquid chromatography.The interleukin-1β(IL-13)content and Caspase-1 relative activity of muscles was determined using the enzyme-linked immune sorbent assay and colorimetric assay.Western blotting was employed to detect the expression of NLRP3,ASC,NF-E2-related factor 2(Nrf2)and quinone oxidase reductase 1(NQO1)protein.Results The ROS generation and the level of 8-oxodG in mtDNA,Caspase-1 activity and IL-1β content,as well as NLRP3 and ASC protein expression in skeletal muscles in group HC were significantly higher than group NC(P＜0.01 for all),while the Nrf2 and NQO1 protein expression of the former were significantly lower than the latter(P＜0.05,P＜0.01).The ROS generation and the level of 8-oxodG in mtDNA,Caspase-1 activity and IL-13 content,as well as NLRP3 and ASC protein expression in skeletal muscle in group HT were significantly lower than group HC(P＜0.05,P＜0.01),while the Nrf2 and NQO1 protein expression of the former were significantly higher than the latter(P＜0.01 for all).Conclusion Exercise training in hypoxia can prevent hypoxia induced NLRP3 inflammasome activation in skeletal muscle via Nrf2-dependent pathways to suppress ROS generation and elevate the expression of antioxidant enzymes.