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.

阻塞性睡眠呼吸暂停（OSA）的主要特点是慢性间歇性缺氧（CIH）并伴有多发性脑损伤。核苷酸寡聚结构域 (NOD) 样受体蛋白 3 (NLRP3) 炎症小体被认为是诱导和维持炎症的最重要因素。然而，NLRP3 在 CIH 引起的神经炎症中的作用及其潜在机制仍不清楚。我们构建了 OSA 相关的 CIH 体内模型，并评估了大鼠在 Morris 水迷宫中的认知行为。通过TargetScan数据库、双荧光素酶报告基因实验和RNA免疫沉淀（RIP）实验证实miR-223-3p与NLRP3的结合。采用Western blot和ELISA法分析靶向NLRP3的miR-223-3p对CIH大鼠体内焦亡或炎症因子表达的影响。治疗后第 6 周，大鼠出现严重认知障碍，血液和海马中炎症因子增加，NLRP3 表达升高，miR-223-3p 水平降低。并通过双荧光素酶报告基因和RIP实验证实了二者良好的结合活性。接下来，我们发现在CIH模型中沉默NLRP3或过度表达miR-223-3p可以改善大鼠的认知缺陷并降低促炎因子和细胞焦亡因子的水平。最后，基于沉默NLRP3或过表达miR-223-3p，我们证实miR-223-3p与NLRP3之间存在调控关系。我们的结果表明 NLRP3/ miR-223-3p 轴在减轻 CIH 诱导的神经炎症中发挥作用。