Astragaloside IV ameliorated neuroinflammation and improved neurological functions in mice exposed to traumatic brain injury by modulating the PERK-eIF2α-ATF4 signaling pathway.

IF 2.5 4区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Journal of Investigative Medicine Pub Date : 2024-10-01 Epub Date: 2024-07-27 DOI:10.1177/10815589241261293
Jianfei Zhao, Gengshui Zhao, Jiadong Lang, Boyu Sun, Shiyao Feng, Dongsheng Li, Guozhu Sun
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引用次数: 0

Abstract

Increasing evidence suggests that endoplasmic reticulum stress (ER stress) and neuroinflammation are involved in the complex pathological process of traumatic brain injury (TBI). However, the pathological mechanisms of their interactions in TBI remain incompletely elucidated. Therefore, investigating and ameliorating neuroinflammation and ER stress post-TBI may represent effective strategies for treating secondary brain injury. Astragaloside IV (AS-IV) has been reported as a potential neuroprotective and anti-inflammatory agent in neurological diseases. This study utilized a mouse TBI model to investigate the pathological mechanisms and crosstalk of ER stress, neuroinflammation, and microglial cell morphology in TBI, as well as the mechanisms and potential of AS-IV in improving TBI. The research revealed that post-TBI, inflammatory factors IL-6, IL-1β, and TNF-α increased, microglial cells were activated, and the specific inhibitor of PERK phosphorylation, GSK2656157, intervened to alleviate neuroinflammation and inhibit microglial cell activation. Post-TBI, levels of ER stress-related proteins (p-PERK, p-eIF2a, ATF4, ATF6, and p-IRE1a) increased. Following AS-IV treatment, neurological dysfunction in TBI mice improved. Levels of p-PERK, p-eIF2a, and ATF4 decreased, along with reductions in inflammatory factors IL-6, IL-1β, and TNF-α. Changes in microglial/macrophage M1/M2 polarization were observed. Additionally, the PERK activator CCT020312 intervention eliminated the impact of AS-IV on post-TBI inflammation and ER stress-related proteins p-PERK, p-eIF2a, and ATF4. These results indicate that AS-IV alleviates neuroinflammation and brain damage post-TBI through the PERK pathway, offering new directions and theoretical insights for TBI treatment.

表达:黄芪皂苷IV通过调节PERK-eIF2α-ATF4信号通路改善脑外伤小鼠的神经炎症并改善其神经功能
越来越多的证据表明,内质网应激(ER 应激)和神经炎症参与了创伤性脑损伤(TBI)的复杂病理过程。然而,它们在创伤性脑损伤中相互作用的病理机制仍未完全阐明。因此,研究和改善创伤性脑损伤后的神经炎症和 ER 应激可能是治疗继发性脑损伤的有效策略。据报道,黄芪皂苷 IV(AS-IV)对神经系统疾病具有潜在的神经保护和抗炎作用。本研究利用小鼠创伤性脑损伤模型,研究创伤性脑损伤的病理机制及ER应激、神经炎症和小胶质细胞形态的相互影响,以及AS-IV改善创伤性脑损伤的机制和潜力。研究发现,创伤性脑损伤后,炎症因子IL-6、IL-1β和TNF-α增加,小胶质细胞被激活,而PERK磷酸化特异性抑制剂GSK2656157的干预缓解了神经炎症,抑制了小胶质细胞的激活。创伤后ER应激相关蛋白(p-PERK、p-eIF2a、ATF4、ATF6和p-IRE1a)水平升高。经过 AS-IV 治疗后,创伤性脑损伤小鼠的神经功能障碍有所改善。p-PERK、p-eIF2a 和 ATF4 的水平下降,炎症因子 IL-6、IL-1β 和 TNF-α 也有所减少。还观察到小胶质细胞/巨噬细胞 M1/M2 极化的变化。此外,PERK 激活剂 CCT020312 的干预消除了 AS-IV 对创伤后炎症和 ER 应激相关蛋白 p-PERK、p-eIF2a 和 ATF4 的影响。这些结果表明,AS-IV 可通过 PERK 通路缓解创伤后神经炎症和脑损伤,为创伤后应激障碍的治疗提供了新的方向和理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Investigative Medicine
Journal of Investigative Medicine 医学-医学:内科
CiteScore
4.90
自引率
0.00%
发文量
111
审稿时长
24 months
期刊介绍: Journal of Investigative Medicine (JIM) is the official publication of the American Federation for Medical Research. The journal is peer-reviewed and publishes high-quality original articles and reviews in the areas of basic, clinical, and translational medical research. JIM publishes on all topics and specialty areas that are critical to the conduct of the entire spectrum of biomedical research: from the translation of clinical observations at the bedside, to basic and animal research to clinical research and the implementation of innovative medical care.
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