Abstract
Obstructive sleep apnea (OSA) is mainly characterized by chronic intermittent hypoxia (CIH) with multiple brain injuries. Nucleotide oligomerization domain (NOD)–like receptor protein 3 (NLRP3) inflammasome is considered the most important factor inducing and maintaining inflammation. However, the role of NLRP3 and its underlying mechanism in CIH-elicited neuroinflammation remains unclear. We constructed an OSA-related CIH in vivo model and assessed the rats’ cognitive behavior in the Morris water maze. The combination of miR-223-3p and NLRP3 was confirmed by the TargetScan database, double luciferase reporter gene experiment, and RNA immunoprecipitation (RIP) experiment. Western blot and ELISA assay were used to analyze the effects of miR-223-3p targeting NLRP3 on the expression of pyroptotic or inflammatory factors in vivo in CIH rats. Severe cognitive impairment was observed in rats at week 6 post-treatment, with increased inflammatory factors in the blood and hippocampus, heightened NLRP3 expression, and low miR-223-3p levels. And the good binding activity of the two was confirmed by dual luciferase reporter and RIP experiments. Next, we found that silencing NLRP3 or overexpression of miR-223-3p in the CIH model could improve cognitive deficits and reduce the level of proinflammatory factors and pyroptosis factors in rats. Finally, based on silencing NLRP3 or overexpression miR-223-3p, we confirmed that there was a regulatory relationship between miR-223-3p and NLRP3. Our results suggested that the NLRP3/ miR-223-3p axis played a role in attenuating CIH-induced neuroinflammation.
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Data availability
The dataset used and/or analyzed in this study is available from the corresponding author on reasonable request.
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Funding
The research was funded by the Provincial Natural Science Foundation Project of Anhui, China (No. 2208085MH232), the Key Natural Science Research Project of Anhui Provincial Department of Education (grant no. KJ2021A0858), and the Young Scientific Research Project Training Fund of Wannan Medical College (WK2022F06).
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LSF conceived and designed the study. C. W., W. X., and Z. Y. X. wrote the main manuscript text and did this experiment and gathered data. J. W., N. Z., F. Q. S., and Q. L. analyzed the data. All authors reviewed the manuscript. All authors read and approved the final manuscript.
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All the experiments were approved by the ethics committee of Wannan Medical College (WNMC-AWE-2023021). No patient was involved in this study.
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The animal experiments were performed following the United States National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publication No. 85–23, revised 1985). The animal protocol was approved by the ethics committee of Wannan Medical College (WNMC-AWE-2023021).
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Wu, C., Xing, W., Zhang, Y. et al. NLRP3/miR-223-3p axis attenuates neuroinflammation induced by chronic intermittent hypoxia. Funct Integr Genomics 23, 342 (2023). https://doi.org/10.1007/s10142-023-01268-w
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DOI: https://doi.org/10.1007/s10142-023-01268-w