Zhang Kuo, Du Yihui, Yang Sihui, Sun Guozhu
Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang City, 050000, Hebei Province, China.
Department of Neurosurgery, Hebei General Hospital, Shijiazhuang City, 050000, Hebei Province, China.
Sci Rep. 2025 May 4;15(1):15583. doi: 10.1038/s41598-025-00066-7.
Irisin is a hormone-like peptide secreted by muscle tissues and generated by hydrolysis of type III fibronectin domain-containing protein 5 by proteolytic hydrolases. Whether Irisin has a potential protective role in traumatic brain injury (TBI). In this study, we will investigate the relevant research progress of Irisin's protective role in traumatic brain injury (TBI) in recent years in terms of attenuating oxidative stress, inhibiting pyroptosis, suppressing inflammatory response, and improving autophagy, with the aim of providing valuable references for the diagnosis and treatment of traumatic brain injury (TBI). Utilize bioinformatics analysis to study the interactions between genes in TBI (Traumatic Brain Injury). Construct a TBI mouse model to observe the effects of Irisin on TBI. The Morris water maze test is used to assess the learning and spatial memory abilities of mice, TUNEL fluorescence is used to detect cell apoptosis, Nissl staining is employed to observe the survival of hippocampal neurons in mice, and HE staining is used to observe the extent of brain injury in mice. Western blot is used to detect protein expression in both in vivo and in vitro experiments. Q-PCR is employed to detect the levels of proteins related to autophagy/pyroptosis/inflammation. Irisin promotes MerTK overexpression by enhancing AMPK activation. Irisin can increase the expression of LC3I and Beclin-1 proteins, indicating the promotion of autophagic response. Additionally, Irisin reduces ROS levels and decreases SYK expression, thereby inhibiting the inflammatory response. Irisin improves the learning and spatial memory abilities of TBI mice and reduces cell apoptosis, as well as decreases hippocampal neuron death. HE staining shows that the brain injury in mice treated with Irisin is significantly alleviated. Irisin can enhance the expression of phosphorylated AMPK and phosphorylated MerTK proteins, promote autophagic response, and inhibit pyroptosis/inflammatory response. Correction experiments confirmed that after stimulation with an AMPK agonist, the expression of phosphorylated MerTK protein is significantly increased, autophagic response is enhanced, and pyroptosis/inflammatory response is weakened. When treated with a MerTK inhibitor during AMPK agonist stimulation, the autophagic response is weakened while pyroptosis/inflammatory response is enhanced. Irisin can inhibit the progression of traumatic brain injury by regulating AMPK/MerTK/autophagy and SYK/ROS/inflammatory signaling.
鸢尾素是一种由肌肉组织分泌的类激素肽，由蛋白水解酶对含III型纤连蛋白结构域蛋白5进行水解产生。鸢尾素在创伤性脑损伤（TBI）中是否具有潜在的保护作用。在本研究中，我们将从减轻氧化应激、抑制细胞焦亡、抑制炎症反应和改善自噬等方面，探讨近年来鸢尾素在创伤性脑损伤（TBI）中的保护作用的相关研究进展，旨在为创伤性脑损伤（TBI）的诊断和治疗提供有价值的参考。利用生物信息学分析研究创伤性脑损伤（TBI）中基因之间的相互作用。构建TBI小鼠模型，观察鸢尾素对TBI的影响。采用Morris水迷宫试验评估小鼠的学习和空间记忆能力，TUNEL荧光法检测细胞凋亡，尼氏染色法观察小鼠海马神经元的存活情况，苏木精-伊红（HE）染色法观察小鼠脑损伤程度。蛋白质免疫印迹法用于体内和体外实验中检测蛋白质表达。实时荧光定量聚合酶链反应（Q-PCR）用于检测与自噬/细胞焦亡/炎症相关的蛋白质水平。鸢尾素通过增强AMPK激活促进MerTK过表达。鸢尾素可增加LC3I和Beclin-1蛋白的表达，表明促进了自噬反应。此外，鸢尾素降低活性氧（ROS）水平并降低SYK表达，从而抑制炎症反应。鸢尾素改善TBI小鼠的学习和空间记忆能力，减少细胞凋亡，并减少海马神经元死亡。HE染色显示，鸢尾素治疗的小鼠脑损伤明显减轻。鸢尾素可增强磷酸化AMPK和磷酸化MerTK蛋白的表达，促进自噬反应，并抑制细胞焦亡/炎症反应。校正实验证实，用AMPK激动剂刺激后，磷酸化MerTK蛋白的表达显著增加，自噬反应增强，细胞焦亡/炎症反应减弱。在AMPK激动剂刺激期间用MerTK抑制剂处理时，自噬反应减弱，而细胞焦亡/炎症反应增强。鸢尾素可通过调节AMPK/MerTK/自噬和SYK/ROS/炎症信号来抑制创伤性脑损伤的进展。
