Ding Mei-Li, Ma Hui, Man Yi-Gang, Lv Hong-Yan
a Department of Pediatrics, Shandong Jining No. 1 People's Hospital, Shandong 272011, China.
b Department of Neurosurgery, Shandong Jining No. 1 People's Hospital, Shandong 272011, China.
Can J Physiol Pharmacol. 2017 Dec;95(12):1396-1405. doi: 10.1139/cjpp-2016-0333. Epub 2017 Jul 5.
Epigallocatechin-3-gallate (EGCG), a polyphenol in green tea, is an effective antioxidant and possesses neuroprotective effects. Brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are crucial for neurogenesis and synaptic plasticity. In this study, we aimed to assess the protective effects of EGCG against sevoflurane-induced neurotoxicity in neonatal mice. Distinct groups of C57BL/6 mice were given EGCG (25, 50, or 75 mg/kg body weight) from postnatal day 3 (P3) to P21 and were subjected to sevoflurane (3%; 6 h) exposure on P7. EGCG significantly inhibited sevoflurane-induced neuroapoptosis as determined by Fluoro-Jade B staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Increased levels of cleaved caspase-3, downregulated Bad and Bax, and significantly enhanced Bcl-2, Bcl-xL, xIAP, c-IAP-1, and survivin expression were observed. EGCG induced activation of the PI3K/Akt pathway as evidenced by increased Akt, phospho-Akt, GSK-3β, phospho-GSK-3β, and mTORc1 levels. Sevoflurane-mediated downregulation of cAMP/CREB and BDNF/TrkB signalling was inhibited by EGCG. Reverse transcription PCR analysis revealed enhanced BDNF and TrkB mRNA levels upon EGCG administration. Improved performance of mice in Morris water maze tests suggested enhanced learning and memory. The study indicates that EGCG was able to effectively inhibit sevoflurane-induced neurodegeneration and improve learning and memory retention of mice via activation of CREB/BDNF/TrkB-PI3K/Akt signalling.
表没食子儿茶素-3-没食子酸酯（EGCG）是绿茶中的一种多酚，是一种有效的抗氧化剂，具有神经保护作用。脑源性神经营养因子（BDNF）和环磷腺苷反应元件结合蛋白（CREB）对神经发生和突触可塑性至关重要。在本研究中，我们旨在评估EGCG对新生小鼠七氟醚诱导的神经毒性的保护作用。将不同组的C57BL/6小鼠从出生后第3天（P3）至P21给予EGCG（25、50或75mg/kg体重），并在P7接受七氟醚（3%；6小时）暴露。通过Fluoro-Jade B染色和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）测定，EGCG显著抑制了七氟醚诱导的神经细胞凋亡。观察到裂解的半胱天冬酶-3水平升高、Bad和Bax下调，以及Bcl-2、Bcl-xL、XIAP、c-IAP-1和survivin表达显著增强。EGCG诱导PI3K/Akt通路的激活，表现为Akt、磷酸化Akt、GSK-3β、磷酸化GSK-3β和mTORc1水平升高。EGCG抑制了七氟醚介导的cAMP/CREB和BDNF/TrkB信号通路的下调。逆转录PCR分析显示给予EGCG后BDNF和TrkB mRNA水平增强。小鼠在莫里斯水迷宫试验中的表现改善表明学习和记忆增强。该研究表明，EGCG能够通过激活CREB/BDNF/TrkB-PI3K/Akt信号通路有效抑制七氟醚诱导的神经退行性变，并改善小鼠的学习和记忆保持能力。
