The nucleotide oligomerization domain (NOD)-like receptor (NLR) pyrin domain-containing protein 1 (NLRP1) inflammasome has been shown to contribute to brain injury after ischemic stroke. Our previous study showed that microRNA-9a-5p (miR-9a-5p) ameliorates ischemic injury by regulating neuronal autophagy in rats subjected to middle cerebral artery occlusion (MCAO) surgery. The aims of this study were to investigate whether miR-9a-5p can influence the NLRP1 inflammasome following ischemic stroke and to clarify the mechanism involved. We found that MCAO in rats increased the level of NLRP1 inflammasome proteins, including NLRP1 receptor, ASC and precursor caspase-1, which induced higher levels of cleaved caspase-1, mature interleukin-1β (IL-1β) and interleukin-18 (IL-18). Similarly, the levels of the NLRP1 inflammasome proteins, cleaved caspase-1, mature IL-1β and IL-18 were elevated in SY-5Y cells exposed to oxygen-glucose deprivation (OGD). Further investigation showed that NLRP1 was a target of miR-9a-5p and was downregulated by miR-9a-5p overexpression and upregulated by miR-9a-5p inhibition. Moreover, overexpression of miR-9a-5p not only decreased the levels of NLRP1, ASC and precursor caspase-1 but also reduced the levels of IL-1β and IL-18 in MCAO rats and OGD cells. Therefore, we conclude that miR-9a-5p is involved in NLRP1 inflammasome-mediated ischemic injury, which further suggests that the overexpression of miR-9 may be an effective way to ameliorate brain injury following ischemic stroke.

核苷酸寡聚化结构域 (NOD) 样受体 (NLR) 含吡啶结构域蛋白 1 (NLRP1) 炎性体已被证明有助于缺血性中风后的脑损伤。我们之前的研究表明，microRNA-9a-5p (miR-9a-5p) 通过调节大脑中动脉闭塞 (MCAO) 手术大鼠的神经元自噬来改善缺血性损伤。本研究的目的是调查 miR-9a-5p 是否可以影响缺血性卒中后的 NLRP1 炎性体，并阐明所涉及的机制。我们发现大鼠中的 MCAO 增加了 NLRP1 炎症小体蛋白的水平，包括 NLRP1 受体、ASC 和前体 caspase-1，从而诱导更高水平的裂解 caspase-1、成熟白细胞介素 1β (IL-1β) 和白细胞介素 18 (IL -18）。同样，NLRP1 炎性体蛋白的水平，裂解的 caspase-1，暴露于氧-葡萄糖剥夺 (OGD) 的 SY-5Y 细胞中成熟的 IL-1β 和 IL-18 升高。进一步的研究表明，NLRP1 是 miR-9a-5p 的靶标，并被 miR-9a-5p 过表达下调，并被 miR-9a-5p 抑制上调。此外，miR-9a-5p的过表达不仅降低了MCAO大鼠和OGD细胞中NLRP1、ASC和前体caspase-1的水平，而且降低了IL-1β和IL-18的水平。因此，我们得出结论，miR-9a-5p 参与了 NLRP1 炎性体介导的缺血性损伤，这进一步表明 miR-9 的过表达可能是改善缺血性卒中后脑损伤的有效方法。进一步的研究表明，NLRP1 是 miR-9a-5p 的靶标，并被 miR-9a-5p 过表达下调，并被 miR-9a-5p 抑制上调。此外，miR-9a-5p的过表达不仅降低了MCAO大鼠和OGD细胞中NLRP1、ASC和前体caspase-1的水平，而且降低了IL-1β和IL-18的水平。因此，我们得出结论，miR-9a-5p 参与了 NLRP1 炎性体介导的缺血性损伤，这进一步表明 miR-9 的过表达可能是改善缺血性卒中后脑损伤的有效方法。进一步的研究表明，NLRP1 是 miR-9a-5p 的靶标，并被 miR-9a-5p 过表达下调，并被 miR-9a-5p 抑制上调。此外，miR-9a-5p的过表达不仅降低了MCAO大鼠和OGD细胞中NLRP1、ASC和前体caspase-1的水平，而且降低了IL-1β和IL-18的水平。因此，我们得出结论，miR-9a-5p 参与了 NLRP1 炎性体介导的缺血性损伤，这进一步表明 miR-9 的过表达可能是改善缺血性卒中后脑损伤的有效方法。