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Effect of the NLRP3 inflammasome on increased hypoxic ventilation response after CIH exposure in mice
Xinyun Jia1, Jianxia Sun1, Qingya Zhuo1
1Department of Respiratory, The First Affiliated Hospital of Xinxiang Medical University, 88 Jiankang Road, Weihui 453100, Henan, China; Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical University, 88 Jiankang Road, Weihui 453100, Henan, China.
Background:
Chronic intermittent hypoxia (CIH) increases the hypoxic ventilation response (HVR). The downstream cytokine IL-1β of the NLRP3 inflammasome regulates respiration by acting on the carotid body (CB) and neurons in the respiratory center, but the effect of the NLRP3 inflammasome on HVR induced by CIH remains unclear.
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.
Conclusion:
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.
