Guo Xin-Bin, Deng Xin, Wang Jingjing, Qi Yuruo, Zhao Wen, Guan Sheng
Department of Neuro-interventional Radiology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe Road, 450052, Zhengzhou, China.
Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, 450001, Zhengzhou, Henan, China.
Cell Death Discov. 2024 May 29;10(1):264. doi: 10.1038/s41420-024-02005-3.
Acute cerebral ischemia has a high rate of disability and death. Although timely recanalization therapy may rescue the ischemic brain tissue, cerebral ischemia-reperfusion injury has been shown to limit the therapeutic effects of vascular recanalization. Protein HAX-1 has been reported as a pro-survival protein that plays an important role in various disorders, particularly in association with the nervous system. However, the effects and mechanisms of HAX-1 in cerebral IR injury have yet to be elucidated. So, we aimed to investigate the effect of HAX-1 on microglial pyroptosis and explore its potential neuroprotective effects in ischemia-reperfusion injury. Our results show that the expression of HAX-1 decreased after cerebral IR injury, accompanied by an increase in pyroptosis pathway activation. In addition, HAX-1 could inhibit microglial pyroptosis both in vivo and in vitro and reduce the release of inflammatory mediators. The above neuroprotective effects might be partially mediated by inhibiting of interaction of NLRP3 and ASC through competitive binding, followed by the attenuation of NLRP3 inflammasome formation. In conclusion, Our findings support that HAX-1 exhibits a protective role in cerebral I/R injury, and further study on HAX-1 expression regulation will contribute to cerebral infarction therapy.
急性脑缺血具有较高的致残率和死亡率。尽管及时的再灌注治疗可能挽救缺血脑组织，但脑缺血再灌注损伤已被证明会限制血管再通的治疗效果。据报道，蛋白质HAX-1是一种促生存蛋白，在各种疾病中发挥重要作用，尤其是与神经系统相关的疾病。然而，HAX-1在脑缺血再灌注损伤中的作用和机制尚未阐明。因此，我们旨在研究HAX-1对小胶质细胞焦亡的影响，并探讨其在缺血再灌注损伤中的潜在神经保护作用。我们的结果表明，脑缺血再灌注损伤后HAX-1的表达降低，同时焦亡途径的激活增加。此外，HAX-1在体内和体外均可抑制小胶质细胞焦亡，并减少炎症介质的释放。上述神经保护作用可能部分是通过竞争性结合抑制NLRP3和ASC的相互作用，进而减弱NLRP3炎性小体的形成来介导的。总之，我们的研究结果支持HAX-1在脑缺血/再灌注损伤中发挥保护作用，对HAX-1表达调控的进一步研究将有助于脑梗死的治疗。
