Zhu Jiayi, Xu Na, Lin Heng, Deng Li, Xie Bingqing, Jiang Xiaoqian, Liao Runde, Yang Chaoxian
Department of Anatomy, School of Basic Medical Sciences, Southwest Medical University, Luzhou, China.
Laboratory of Neurological Diseases and Brain Function, the Affiliated Hospital of Southwest Medical University, Luzhou, China.
Heliyon. 2024 Oct 10;10(20):e39076. doi: 10.1016/j.heliyon.2024.e39076. eCollection 2024 Oct 30.
Remote ischemic preconditioning (RIPC) represents a clinically feasible method for safeguarding vital organs against ischemic injury. However, its specific role in cerebral ischemia-reperfusion (I/R) injury remains to be definitively elucidated. In this study, we investigated the neuroprotective effects of RIPC on mice at 7 days post-cerebral I/R and its involvement in mitophagy and mitochondrial dysfunction. Cerebral I/R led to impaired brain function, as well as structural and functional damage to mitochondria. Notably, RIPC treatment ameliorated the neurological dysfunction induced by cerebral I/R. Compared with the I/R group, the expression levels of NeuN, MBP, PDH, and Tom20 were significantly elevated in the RIPC + I/R group. Furthermore, mitochondria in the RIPC + I/R group exhibited more intact structure compared to those in the I/R group. In mice subjected to I/R injury, RIPC treatment markedly increased ATP content, ADP content, TAN level and glucose uptake while upregulating expression levels of Parkin, Pink1 and P62 proteins; it also reduced both the volume of ischemic foci and the number of mitochondrial autophagosomes along with decreasing LC3B II/I ratio. In conclusion, RIPC may exert a neuroprotective role by inhibiting excessive mitophagy during subacute stages following an ischemic stroke.
远程缺血预处理（RIPC）是一种临床上可行的保护重要器官免受缺血性损伤的方法。然而，其在脑缺血再灌注（I/R）损伤中的具体作用仍有待明确阐明。在本研究中，我们研究了RIPC对脑I/R后7天小鼠的神经保护作用及其与线粒体自噬和线粒体功能障碍的关系。脑I/R导致脑功能受损以及线粒体的结构和功能损伤。值得注意的是，RIPC治疗改善了脑I/R诱导的神经功能障碍。与I/R组相比，RIPC + I/R组中NeuN、MBP、PDH和Tom20的表达水平显著升高。此外，与I/R组相比，RIPC + I/R组中的线粒体结构更完整。在遭受I/R损伤的小鼠中，RIPC治疗显著增加了ATP含量、ADP含量、TAN水平和葡萄糖摄取，同时上调了Parkin、Pink1和P62蛋白的表达水平；它还减少了缺血灶的体积和线粒体自噬体的数量，并降低了LC3B II/I比率。总之，RIPC可能通过在缺血性中风后的亚急性期抑制过度的线粒体自噬发挥神经保护作用。
