Hao Liang, Zhang Aobo, Lv Dongsheng, Cong LuLu, Sun Zhimin, Liu Liqiang
Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
Department of Neurosurgery, The Third Hospital of Shijiazhuang, Shijiazhuang, 050000, Hebei, China.
Sci Rep. 2024 Dec 28;14(1):31474. doi: 10.1038/s41598-024-82938-y.
Intracerebral hemorrhage (ICH) is a common cerebrovascular disease characterized by a high incidence, disability rate, and mortality. Epigallocatechin gallate (EGCG), a key catechin compound found in green tea, has received increasing attention for its potential neuroprotective and therapeutic effects in neurological disorders. Studies have indicated that EGCG may influence various signaling pathways and molecular targets, including the inhibition of oxidative stress, reduction of inflammatory responses, suppression of cell apoptosis, regulation of cell survival, and enhancement of autophagy. Although the exact mechanism of action of EGCG is not fully understood, it has become a focal point of research in various disciplines due to its promising potential. This study aims to investigate the effects of EGCG on oxidative stress, iron deposition, and cell apoptosis in rats with ICH, as well as to uncover the underlying mechanisms. An ICH rat model was created to simulate cerebral hemorrhage, while an in vitro model utilizing primary cortical neurons was developed. The neurons were pre-treated with EGCG before being exposed to Erastin and RSL3 to induce iron death. The levels of oxidative stress, iron deposition, and cell apoptosis were evaluated in both models. In the ICH model, EGCG was discovered to enhance the activation of the Keap1/P62/Nrf2 signaling pathway in both in vivo and in vitro studies. Furthermore, EGCG significantly elevated the levels of GPX4 and XCT proteins, as well as the nuclear expression of Nrf2. It was noted that the Nrf2 inhibitor ML385 partially decreased the expression of these proteins. Through the activation of the Keap1/P62/Nrf2 pathway, EGCG inhibits inflammation, oxidative stress and iron deposition in rats with cerebral hemorrhage. EGCG inhibits oxidative stress, iron deposition and apoptosis in rats with ICH by activating Keap1/P62/Nrf2 pathway.
脑出血（ICH）是一种常见的脑血管疾病，具有高发病率、致残率和死亡率的特点。表没食子儿茶素没食子酸酯（EGCG）是绿茶中发现的一种关键儿茶素化合物，因其在神经系统疾病中的潜在神经保护和治疗作用而受到越来越多的关注。研究表明，EGCG可能影响多种信号通路和分子靶点，包括抑制氧化应激、减轻炎症反应、抑制细胞凋亡、调节细胞存活以及增强自噬。尽管EGCG的确切作用机制尚未完全明确，但由于其有前景的潜力，已成为各学科研究的焦点。本研究旨在探讨EGCG对脑出血大鼠氧化应激、铁沉积和细胞凋亡的影响，并揭示其潜在机制。建立脑出血大鼠模型以模拟脑出血，同时构建利用原代皮质神经元的体外模型。在暴露于艾拉司群和RSL3诱导铁死亡之前，先用EGCG预处理神经元。在两种模型中评估氧化应激、铁沉积和细胞凋亡水平。在脑出血模型中，体内和体外研究均发现EGCG可增强Keap1/P62/Nrf2信号通路的激活。此外，EGCG显著提高了GPX4和XCT蛋白水平以及Nrf2的核表达。值得注意的是，Nrf2抑制剂ML385部分降低了这些蛋白的表达。通过激活Keap1/P62/Nrf2通路，EGCG抑制脑出血大鼠的炎症、氧化应激和铁沉积。EGCG通过激活Keap1/P62/Nrf2通路抑制脑出血大鼠的氧化应激、铁沉积和细胞凋亡。
