Department of Anesthesiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Anesthesiology, The First People's Hospital of Foshan, Foshan, Guangdong, China.
CNS Neurosci Ther. 2024 Feb;30(2):e14373. doi: 10.1111/cns.14373. Epub 2023 Jul 27.
Elderly patients often exhibit postoperative cognitive dysfunction (POCD), a postsurgical decline in memory and executive function. Oxidative stress and neuroinflammation, both pathological characteristics of the aged brain, contribute to this decline. This study posits that electroacupuncture (EA) stimulation, an effective antioxidant and anti-inflammatory modality, may enhance telomerase reverse transcriptase (TERT) function, the catalytic subunit of telomerase known for its protective properties against cellular senescence and oxidative damage, to alleviate POCD in aged mice.
The animal POCD model was created by subjecting aged mice to abdominal surgery, followed by EA pretreatment at the Baihui acupoint (GV20). Postoperative cognitive function was gauged using the Morris water maze (MWM) test. Hippocampal TERT mRNA levels and telomerase activity were determined through qPCR and a Telomerase PCR ELISA kit, respectively. Oxidative stress was assessed through superoxide dismutase (SOD), reactive oxygen species (ROS), and malondialdehyde (MDA) levels. Iba-1 immunostaining determined the quantity of hippocampal microglia. Additionally, western blotting assessed TERT, autophagy markers, and proinflammatory cytokines at the protein level.
Abdominal surgery in aged mice significantly decreased telomerase activity and TERT mRNA and protein levels, but increased oxidative stress and neuroinflammation and decreased autophagy in the hippocampus. EA-pretreated mice demonstrated improved postoperative cognitive performance, enhanced telomerase activity, increased TERT protein expression, improved TERT mitochondrial localization, and reduced oxidative damage, autophagy dysfunction, and neuroinflammation. The neuroprotective benefits of EA pretreatment were diminished following TERT knockdown.
Our findings underscore the significance of TERT function preservation in alleviating surgery-induced oxidative stress and neuroinflammation in aged mice. A novel neuroprotective mechanism of EA stimulation is highlighted, whereby modulation of TERT and telomerase activity reduces oxidative damage and neuroinflammation. Consequently, maintaining TERT function via EA treatment could serve as an effective strategy for managing POCD in elderly patients.
老年患者常表现出术后认知功能障碍（POCD），即术后记忆力和执行功能下降。氧化应激和神经炎症是衰老大脑的病理特征，都会导致这种下降。本研究假设电针（EA）刺激作为一种有效的抗氧化和抗炎方式，可能会增强端粒酶逆转录酶（TERT）的功能，TERT 是端粒酶的催化亚基，因其对细胞衰老和氧化损伤的保护作用而闻名。这种方式可能会缓解老年小鼠的 POCD。
通过对老年小鼠进行腹部手术，然后在百会穴（GV20）进行电针预处理，建立动物 POCD 模型。术后认知功能通过 Morris 水迷宫（MWM）测试进行评估。通过 qPCR 和端粒酶 PCR ELISA 试剂盒分别测定海马 TERT mRNA 水平和端粒酶活性。通过超氧化物歧化酶（SOD）、活性氧（ROS）和丙二醛（MDA）水平评估氧化应激。Iba-1 免疫染色测定海马小胶质细胞的数量。此外，通过 Western blot 评估 TERT、自噬标志物和促炎细胞因子的蛋白水平。
腹部手术使老年小鼠的端粒酶活性和 TERT mRNA 及蛋白水平显著降低，但增加了海马中的氧化应激、神经炎症和自噬功能障碍。电针预处理的小鼠术后认知表现得到改善，端粒酶活性增强，TERT 蛋白表达增加，TERT 线粒体定位改善，氧化损伤、自噬功能障碍和神经炎症减少。TERT 敲低后，电针预处理的神经保护作用减弱。
我们的研究结果强调了 TERT 功能在缓解老年小鼠手术引起的氧化应激和神经炎症中的重要性。本研究突出了 EA 刺激的一种新的神经保护机制，即通过调节 TERT 和端粒酶活性减轻氧化损伤和神经炎症。因此，通过 EA 治疗维持 TERT 功能可能是治疗老年患者 POCD 的有效策略。
