HLY78 Attenuates Neuronal Apoptosis via the LRP6/GSK3β/β-Catenin Signaling Pathway After Subarachnoid Hemorrhage in Rats
HLY78 Attenuates Neuronal Apoptosis via the LRP6/GSK3β/β-Catenin Signaling Pathway After Subarachnoid Hemorrhage in Rats
复制标题
HLY78 通过 LRP6/GSK3p/p-Catenin 信号通路减轻大鼠蛛网膜下腔出血后的神经元凋亡
DOI：
10.1007/s12264-020-00532-4
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发表时间：
2020-06-20
影响因子：
5.6
通讯作者：
Xie, Zongyi
中科院分区：
文献类型：
--
作者：
Luo, Xu;Li, Lina;Xie, Zongyi
神经细胞凋亡是蛛网膜下腔出血(SAH)后早期脑损伤的重要机制之一。最近，HLY78被证明通过激活Wnt/β-catenin途径来抑制碳离子辐射引起的肿瘤细胞和胚胎细胞的凋亡。本研究旨在探讨HLY78对实验性蛛网膜下腔出血的抗细胞凋亡作用。结果表明，HLY78通过激活低密度脂蛋白受体相关蛋白6(LRP6)，进而增加磷酸化糖原合成蛋白3β(p-GSK3β)(Ser9)、β-连环蛋白(β-catenin)和bc l-2水平，同时降低p-β-catenin、Bax和裂解caspase 3，从而减轻SAH后神经细胞的凋亡和神经功能障碍。综上所述，HLY78通过LRP6/GSK3β/β-catenin信号通路减轻SAH大鼠神经细胞凋亡，改善神经功能障碍。HLY78是一种有前景的治疗SAH后早期脑损伤的药物。
Neuronal apoptosis is one of the essential mechanisms of early brain injury after subarachnoid hemorrhage (SAH). Recently, HLY78 has been shown to inhibit apoptosis in tumor cells and embryonic cells caused by carbon ion radiation through activation of the Wnt/beta-catenin pathway. This study was designed to explore the anti-apoptotic role of HLY78 in experimental SAH. The results demonstrated that HLY78 attenuated neuronal apoptosis and the neurological deficits after SAH through the activation of low-density lipoprotein receptor-related protein 6 (LRP6), which subsequently increased the level of phosphorylated glycogen synthesis kinase 3 beta (p-GSK3 beta) (Ser9), beta-catenin, and Bcl-2, accompanied by a decrease of p-beta-catenin, Bax, and cleaved caspase 3. An LRP6 small-interfering ribonucleic acid reversed the effects of HLY78. In conclusion, HLY78 attenuates neuronal apoptosis and improves neurological deficits through the LRP6/GSK3 beta/beta-catenin signaling pathway after SAH in rats. HLY78 is a promising therapeutic agent to attenuate early brain injury after SAH.