Duan Pengyu, Li Xiaoyan, Bi Yonghong, Feng Weiyu, Jin Zhehao, Zhang Xiaoqian, He Guanghui, An Da, Wen Zhibin, Zhang Bing
Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang Province, China.
The Key Laboratory of Anesthesiology and Intensive Care Research of Heilongjiang Province, Harbin, China.
Sci Rep. 2025 Jan 6;15(1):905. doi: 10.1038/s41598-024-84948-2.
Cardiopulmonary resuscitation (CPR) after cardiac arrest (CA) is an important cause of neurological impairment and leads to considerable morbidity and mortality. The stability of the blood-brain barrier (BBB) is crucial for minimizing secondary neurological damage and improving long-term prognosis. However, the precise mechanisms and regulatory pathways that contribute to BBB dysfunction after CPR remain elusive. GYY4137 is an innovative hydrogen sulfide slow-release agent with excellent properties as a hydrogen sulfide substitute. The aim of this study was to investigate the protective effects of GYY4137 on CA/CPR and the underlying mechanisms of BBB protection. The effects of GYY4137 on systemic inflammation, BBB integrity, and autophagy were evaluated using a mouse CA/CPR model. The underlying mechanisms of occludin changes associated with GYY4137 were investigated using oxygen-glucose deprivation / reoxygenation (OGD/R) model. ELISA, neurological function and other tests showed that GYY4137 ameliorates systemic inflammation and neurological prognosis. Western blotting, transwell migration and tube formation assays showed that GYY4137 improves BBB function both in vivo and in vitro. The detection of autophagy flow and protein degradation pathways showed the inhibition of occludin reduction by GYY4137 was mainly achieved by suppressing autophagy mediated degradation. Taken together, GYY4137 may improve BBB dysfunction following CPR by increasing occludin content. This effect was achieved by inhibiting autophagic degradation rather than promoting synthesis. GYY4137 also mitigated systemic inflammation and improved neurological outcomes after CA/CPR. In summary, our study provides valuable insights into protecting the integrity of BBB and improving neurological outcomes after CPR.
心脏骤停（CA）后的心肺复苏（CPR）是导致神经功能障碍的重要原因，并会引发相当高的发病率和死亡率。血脑屏障（BBB）的稳定性对于将继发性神经损伤降至最低并改善长期预后至关重要。然而，心肺复苏后导致血脑屏障功能障碍的精确机制和调控途径仍不清楚。GYY4137是一种创新的硫化氢缓释剂，作为硫化氢替代品具有优异的性能。本研究的目的是探讨GYY4137对心脏骤停/心肺复苏的保护作用以及血脑屏障保护的潜在机制。使用小鼠心脏骤停/心肺复苏模型评估GYY4137对全身炎症、血脑屏障完整性和自噬的影响。使用氧糖剥夺/复氧（OGD/R）模型研究与GYY4137相关的闭合蛋白变化的潜在机制。酶联免疫吸附测定、神经功能和其他测试表明，GYY4137可改善全身炎症和神经预后。蛋白质免疫印迹法、transwell迁移和管形成试验表明，GYY4137在体内和体外均可改善血脑屏障功能。自噬流和蛋白质降解途径的检测表明，GYY4137对闭合蛋白减少的抑制主要是通过抑制自噬介导的降解来实现的。综上所述，GYY4137可能通过增加闭合蛋白含量来改善心肺复苏后的血脑屏障功能障碍。这种作用是通过抑制自噬降解而不是促进合成来实现的。GYY4137还减轻了全身炎症并改善了心脏骤停/心肺复苏后的神经结局。总之，我们的研究为保护血脑屏障完整性和改善心肺复苏后的神经结局提供了有价值的见解。
