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表儿茶素通过靶向 AKT-P53/CREB 通路改善创伤性脑损伤的预后。

Targeting the AKT-P53/CREB pathway with epicatechin for improved prognosis of traumatic brain injury.

机构信息

Department of Neurosurgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.

Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.

出版信息

CNS Neurosci Ther. 2024 Feb;30(2):e14364. doi: 10.1111/cns.14364. Epub 2023 Jul 18.

Abstract

AIMS

The aim of this study was to evaluate the effect of epicatechin, on neurological recovery and neuroinflammation after traumatic brain injury (TBI) to investigate its potential value in clinical practice.

METHODS

TBI model was established in adult rats by CCI method. The effect of epicatechin was evaluated after intraperitoneal injection. Neurological recovery after TBI was assessed by Morris Water Maze, mNSS score, Rotarod test and Adhesive removal test. Protein and gene expression was assessed by Western blot, ELISA, PCR and immunofluorescence. Furthermore, the use of AKT pathway inhibitors blocked the therapeutic effects of epicatechin clarifying AKT-P53/CREB as a potential pathway for the effects of epicatechin.

RESULTS

Administering epicatechin after TBI prevented neuronal death, reduced neuroinflammation, and promoted neurological function restoration in TBI rats. Network pharmacology study suggested that epicatechin may exert its therapeutic benefits through the AKT-P53/CREB pathway CONCLUSION: These results indicate that epicatechin, a monomeric compound derived from tea polyphenols, possesses potent antioxidant and anti-inflammatory properties after TBI. The mechanism may be related to the regulation of the AKT-P53/CREB signal pathway.

摘要

目的

本研究旨在评估表儿茶素对创伤性脑损伤(TBI)后神经功能恢复和神经炎症的影响,探讨其在临床实践中的潜在价值。

方法

采用 CCI 法建立成年大鼠 TBI 模型,腹腔注射表儿茶素后评估其作用。通过 Morris 水迷宫、mNSS 评分、转棒试验和粘贴去除试验评估 TBI 后神经功能恢复情况。采用 Western blot、ELISA、PCR 和免疫荧光法评估蛋白和基因表达。此外,使用 AKT 通路抑制剂阻断表儿茶素的治疗作用,阐明 AKT-P53/CREB 作为表儿茶素作用的潜在通路。

结果

TBI 后给予表儿茶素可预防神经元死亡,减轻神经炎症,促进 TBI 大鼠神经功能恢复。网络药理学研究表明,表儿茶素可能通过 AKT-P53/CREB 通路发挥治疗作用。

结论

这些结果表明,表儿茶素作为一种源自茶多酚的单体化合物,在 TBI 后具有强大的抗氧化和抗炎作用。其机制可能与 AKT-P53/CREB 信号通路的调节有关。

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