Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
Department of Nephrology, The Third Affiliated Hospital, Chongqing Medical University, Chongqing 401120, China.
Brain Res Bull. 2020 Sep;162:107-114. doi: 10.1016/j.brainresbull.2020.06.003. Epub 2020 Jun 18.
Wnt/β-catenin signaling plays an essential role in blood-brain barrier (BBB) formation and maintenance under pathophysiological conditions. HLY78, a lycorine derivative, has been identified as a novel activator of Wnt/β-catenin signaling in vitro. However, the effects of HLY78 on the BBB function in subarachnoid hemorrhage (SAH) are not yet validated. The present study was designed to investigate the impacts of HLY78 on the BBB in an endovascular perforation induced SAH model of Sprague-Dawley rats. Western blot, immunofluorescence staining, neurological function, brain water content, and Evans blue assay were performed after SAH induction. The results revealed that the expression of phosphorylated low-density lipoprotein receptor-related protein 6 (p-LRP6) was significantly increased after SAH and further augmented by HLY78. Administration of HLY78 significantly improved neurobehavioral functions and attenuated BBB leakage following SAH. Moreover, HLY78 markedly increased the β-catenin expression followed with the up-regulation of Occludin, ZO-1, and Claudin-5 after SAH, which was reversed by LRP6 siRNA. In conclusion, HLY78 could preserve BBB integrity, possibly through the Wnt/β-catenin signaling pathway. HLY78 might be a potential treatment option to protect BBB integrity following SAH.
Wnt/β-catenin 信号通路在病理生理条件下对血脑屏障（BBB）的形成和维持起着至关重要的作用。HLY78 是一种石蒜碱衍生物，已被鉴定为体外 Wnt/β-catenin 信号通路的新型激活剂。然而，HLY78 对蛛网膜下腔出血（SAH）中 BBB 功能的影响尚未得到验证。本研究旨在探讨 HLY78 对 Sprague-Dawley 大鼠血管内穿孔诱导的 SAH 模型中 BBB 的影响。在诱导 SAH 后进行 Western blot、免疫荧光染色、神经功能、脑水含量和 Evans 蓝测定。结果表明，SAH 后磷酸化低密度脂蛋白受体相关蛋白 6（p-LRP6）的表达明显增加，HLY78 进一步增强了其表达。HLY78 给药可显著改善 SAH 后的神经功能，并减轻 BBB 渗漏。此外，HLY78 明显增加了β-catenin 的表达，随后在 SAH 后上调了 Occludin、ZO-1 和 Claudin-5，而 LRP6 siRNA 则逆转了这一作用。总之，HLY78 可以保护 BBB 的完整性，可能是通过 Wnt/β-catenin 信号通路。HLY78 可能是一种保护 SAH 后 BBB 完整性的潜在治疗选择。
