OBJECTIVE: To investigate the effect of NLRP3 on the increased HVR and spontaneous apnea events and duration induced by CIH, the expression and localization of NLRP3 in the respiratory regulatory center of the rostral ventrolateral medulla (RVLM), and the effect of CIH on the activation of the NLRP3 inflammasome in the RVLM.
METHODS: Eighteen male, 7-week-old C57BL/6 N mice and eighteen male, 7-week-old C57BL/6 N NLRP3 knockout mice were randomly divided into CON-WT, CON-NLRP3-/-, CIH-WT and CIH-NLRP3-/- groups. Respiratory changes in mice were continuously detected using whole-body plethysmography. The expression and localization of the NLRP3 protein and the formation of apoptosis-associated speck-like protein containing CARD (ASC) specks were detected using immunofluorescence staining.
RESULTS: NLRP3 knockout reduced the increased HVR and the incidence and duration of spontaneous apnea events associated with CIH. The increase in HVR caused by CIH partially recovered after reoxygenation. After CIH, NLRP3 inflammasome activation in the RVLM, which is related to respiratory regulation after hypoxia, increased, which was consistent with the trend of the ventilation response.
CONCLUSIONS: The NLRP3 inflammasome may be involved in the increase in the HVR and the incidence and duration of spontaneous apnea induced by CIH. NLRP3 inhibitors may help reduce the increase in the HVR after CIH, which is important for ensuring sleep quality at night in patients with obstructive sleep apnea.
目的:为了研究NLRP3对CIH引起的HVR增加和自发性呼吸暂停事件和持续时间的影响,NLRP3在延髓腹外侧端呼吸调节中枢(RVLM)的表达和定位,以及CIH对RVLM中NLRP3炎性体激活的影响。
方法:18名男性,7周龄C57BL/6N小鼠和18只雄性,将7周龄的C57BL/6NNLRP3基因敲除小鼠随机分为CON-WT,CON-NLRP3-/-,CIH-WT和CIH-NLRP3-/-基团。使用全身体积描记术连续检测小鼠的呼吸变化。使用免疫荧光染色检测NLRP3蛋白的表达和定位以及含有CARD(ASC)斑点的凋亡相关斑点样蛋白的形成。
结果:NLRP3基因敲除降低了HVR的增加以及与CIH相关的自发性呼吸暂停事件的发生率和持续时间。复氧后CIH引起的HVR增加部分恢复。CIH之后,RVLM中的NLRP3炎性体激活,这与缺氧后的呼吸调节有关,增加,这与通气反应的趋势一致。
结论:NLRP3炎性体可能与HVR的增加以及CIH引起的自发性呼吸暂停的发生率和持续时间有关。NLRP3抑制剂可能有助于降低CIH后HVR的增加,这对于确保阻塞性睡眠呼吸暂停患者晚上的睡眠质量很重要。