Department of Pharmacy, Tianjin Medical University, Tianjin, China.
WIMM, University of Oxford, Oxford, United Kingdom.
PLoS One. 2023 Aug 14;18(8):e0290015. doi: 10.1371/journal.pone.0290015. eCollection 2023.
Blood-brain barrier (BBB) leakage is an important cause of the exacerbation of pathological features of cerebral ischemia reperfusion injury (CIRI). However, the specific mechanism of BBB leakage is not clear. It was found that the CIRI resulted in RIPK1 activation and subsequent RIPK1-dependent apoptosis (RDA). Inhibition of RIPK1 significantly reduced BBB breakdown and brain damage. The aim of this study is to investigate the mechanism of RIPK1 in the BBB leakage during CIRI. It was discovered by proteomics that autophagy activation resulting from ischemia and reperfusion significantly downregulated the level of A20 protein. A20 is an important protein that regulates RIPK1 and RDA. It was hypothesized that activation of autophagy caused by ischemic reperfusion led to a decrease in A20 protein, which, in turn, caused the activation of RIPK1 and the occurrence of RDA, leading to leakage of the BBB. The findings in this study revealed the role of RIPK1 in the cell death and BBB leakage upon cerebral ischemia reperfusion injury, and these findings provide a novel perspective for the treatment of ischemic reperfusion.
血脑屏障（BBB）渗漏是导致脑缺血再灌注损伤（CIRI）病理特征恶化的重要原因。然而，BBB 渗漏的确切机制尚不清楚。研究发现，CIRI 导致 RIPK1 激活，进而引发 RIPK1 依赖性细胞凋亡（RDA）。抑制 RIPK1 可显著减少 BBB 破坏和脑损伤。本研究旨在探讨 RIPK1 在 CIRI 期间 BBB 渗漏中的作用机制。通过蛋白质组学发现，缺血再灌注引起的自噬激活显著降低了 A20 蛋白的水平。A20 是一种重要的调节 RIPK1 和 RDA 的蛋白。研究假设缺血再灌注引起的自噬激活导致 A20 蛋白减少，进而导致 RIPK1 激活和 RDA 发生，导致 BBB 渗漏。本研究的结果揭示了 RIPK1 在脑缺血再灌注损伤后细胞死亡和 BBB 渗漏中的作用，为缺血再灌注治疗提供了新的视角。
