连云港市第一人民医院孙勇团队的研究显示，WNK1减轻氯化物外排诱导的NLRP3炎性体激活和蛛网膜下腔出血后早期脑损伤的后续神经炎症。相关论文于2025年5月27日发表在《神经科学通报》杂志上。

在本研究中，该研究团队建立了大鼠/小鼠体内SAH模型，并在脑室内注射AAV-WNK1，以研究其神经保护机制。在SAH患者血液和SAH模型脑组织中，WNK1表达显著降低，与小胶质细胞激活呈负相关。AAV-WNK1通过抑制NLRP3炎性体激活，减轻脑水肿、神经元坏死、行为缺陷和炎症。在hemin刺激的BV-2细胞中，WNK1过表达降低了NLRP3的激活和炎症因子。氯化物抵消了WNK1的抑制作用，WNK1抑制了P2X7R诱导的NLRP3激活。机制上，WNK1通过OXSR1/STK39途径发挥作用。这些发现强调了WNK1作为细胞内氯化物平衡和神经炎症的关键调节因子，提出了SAH治疗的潜在治疗靶点。

据悉，含有3（NLRP3）炎性体的淋巴结样受体家族pyrin结构域在蛛网膜下腔出血（SAH）的预后中起着至关重要的作用。WNK1激酶在各种炎症条件下负调控NLRP3，但其在SAH后早期脑损伤（EBI）中的作用尚不清楚。

附：英文原文

Title: WNK1 Alleviates Chloride Efflux-Induced NLRP3 Inflammasome Activation and Subsequent Neuroinflammation in Early Brain Injury Following Subarachnoid Hemorrhage

Author: Zhao, Panpan, Feng, Huimiao, Zhou, Xinyu, Zhou, Jingyuan, Hu, Fangbo, Hu, Taotao, Sun, Yong

Issue&Volume: 2025-05-27

Abstract: The nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays a crucial role in the prognosis of subarachnoid hemorrhage (SAH). WNK1 kinase negatively regulates NLRP3 in various inflammatory conditions, but its role in early brain injury (EBI) after SAH remains unclear. In this study, we used an in vivo SAH model in rats/mice and AAV-WNK1 intraventricular injection to investigate its neuroprotective mechanisms. WNK1 expression was significantly reduced in SAH patient blood and SAH model brain tissue, correlating negatively with microglial activation. AAV-WNK1 alleviated brain edema, neuronal necrosis, behavioral deficits, and inflammation by inhibiting NLRP3 inflammasome activation. In hemin-stimulated BV-2 cells, WNK1 overexpression reduced NLRP3 activation and inflammatory cytokines. Chloride counteracted WNK1’s inhibitory effects, and WNK1 suppressed P2X7R-induced NLRP3 activation. Mechanistically, WNK1 functioned via the OXSR1/STK39 pathway. These findings highlight WNK1 as a key regulator of intracellular chloride balance and neuroinflammation, presenting a potential therapeutic target for SAH treatment.

DOI: 10.1007/s12264-025-01414-3

Source: https://link.springer.com/article/10.1007/s12264-025-01414-3