Electroacupuncture Ameliorates Neuronal Damage and Neurological Deficits after Cerebral Ischemia-Reperfusion Injury via Restoring Telomerase Reverse Transcriptase.

IF 1.8 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Biochemistry and Biophysics Pub Date : 2024-09-05 DOI:10.1007/s12013-024-01504-5

Dan Chen, Yunxia Xiang, Di Wu, Hui Wang, Yaping Huang, Hongbo Xiao

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Abstract

The purpose of this study is to identify the therapeutic effect of electroacupuncture (EA) on cerebral ischemia-reperfusion (I/R) injury, and to clarify the regulatory mechanism related to telomerase reverse transcriptase (TERT)-mediated telomerase activity. A Middle cerebral artery occlusion/reperfusion (MCAO/R) animal model was constructed and rats were treated by EA invention at the Baihui (GV20) and Fengchi (GB20) acupoints. Neurological deficits were assessed via rotarod test and Morris water maze test. 2,3,5-Triphenyltertrazolium chloride (TTC) staining was performed to evaluate infarct volume. Histological changes were observed under H&E staining and Nissl staining. TERT expression was examined using qRT-PCR and western blot. Telomerase activity was assessed with TRAP method. Neuron apoptosis and senescence were assessed by TUNEL and immunofluorescence assays. Inflammatory cytokines and oxidative stress-indicators were examined using commercial kits. EA intervention at both GV20 and GB20 acupoints reduced infarct volumes (2.48 ± 1.89 vs. 29.56 ± 2.55), elevated the telomerase activity (0.84 ± 0.08 vs. 0.34 ± 0.09), and upregulated the levels of total TERT protein (0.61 ± 0.09 vs. 0.21 ± 0.05) and mitochondrial TERT (Mito-TERT; 0.54 ± 0.03 vs. 0.27 ± 0.03) in hippocampus tissues of MCAO/R rats. EA intervention attenuated motor dysfunction (112.00 ± 6.69 vs. 30.02 ± 2.60) and improved spatial learning (23.87 ± 1.90 vs. 16.23 ± 1.45) and memory ability (8.38 ± 1.06 vs. 4.13 ± 1.13) of rats with cerebral I/R injury. In addition, EA intervention significantly attenuated histopathological changes of injured neurons, mitigated neuron apoptosis (32.27 ± 5.52 vs. 65.83 ± 4.31) and senescence in MCAO/R rats, as well as inhibited excessive production of inflammatory cytokines and attenuated oxidative stress. However, the above therapeutic efficiency of EA intervention in MCAO/R rats was partly eliminated by TERT knockdown. EA intervention at GB20 and GV20 acupoints exerted a protective role in cerebral I/R injury partly through restoring TERT function, implying the clinical potential of EA treatment in the treatment of ischemic stroke.

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电针通过恢复端粒酶逆转录酶改善脑缺血再灌注损伤后的神经元损伤和神经功能缺损

本研究旨在明确电针（EA）对脑缺血再灌注（I/R）损伤的治疗作用，并阐明端粒酶逆转录酶（TERT）介导的端粒酶活性的调控机制。研究人员构建了大脑中动脉闭塞再灌注（MCAO/R）动物模型，并对大鼠进行了百会穴（GV20）和风池穴（GB20）的EA发明治疗。通过旋转木马测试和莫里斯水迷宫测试评估大鼠的神经功能缺损情况。2,3,5-三苯基氯化三氮唑（TTC）染色用于评估梗死体积。通过H&E染色和Nissl染色观察组织学变化。使用 qRT-PCR 和 Western 印迹检测 TERT 的表达。用TRAP法评估端粒酶活性。神经元凋亡和衰老通过 TUNEL 和免疫荧光检测进行评估。炎症细胞因子和氧化应激指标通过商业试剂盒进行检测。在 GV20 和 GB20 穴位进行 EA 干预可减少梗死体积（2.48 ± 1.89 vs. 29.56 ± 2.55），提高端粒酶活性（0.84 ± 0.08 vs. 0.34 ± 0.09），并上调了 MCAO/R 大鼠海马组织中总 TERT 蛋白（0.61 ± 0.09 vs. 0.21 ± 0.05）和线粒体 TERT（Mito-TERT；0.54 ± 0.03 vs. 0.27 ± 0.03）的水平。EA干预可减轻运动功能障碍（112.00 ± 6.69 vs. 30.02 ± 2.60），改善脑I/R损伤大鼠的空间学习能力（23.87 ± 1.90 vs. 16.23 ± 1.45）和记忆能力（8.38 ± 1.06 vs. 4.13 ± 1.13）。此外，EA干预还能明显减轻MCAO/R大鼠损伤神经元的组织病理学变化，缓解神经元凋亡（32.27 ± 5.52 vs. 65.83 ± 4.31）和衰老，以及抑制炎症细胞因子的过度产生和减轻氧化应激。然而，EA干预MCAO/R大鼠的上述治疗效果因TERT敲除而部分消失。GB20和GV20穴位的EA干预在一定程度上通过恢复TERT的功能对脑I/R损伤起到保护作用，这意味着EA治疗在缺血性脑卒中治疗中具有临床潜力。

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来源期刊

Cell Biochemistry and Biophysics 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

7.5 months

期刊介绍： Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.

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