Zhang Yibing, Zhao Yong, Ran Yongwang, Guo Jianyou, Cui Haifeng, Liu Sha
Comprehensive Teaching and Research Office of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 401331, People's Republic of China.
GLP Laboratory, Institute of Chinese Materia Medica, China Academy of Traditional Chinese Medicine, Beijing, 100700, People's Republic of China.
Transl Neurosci. 2020 Jun 22;11(1):215-226. doi: 10.1515/tnsci-2020-0118. eCollection 2020.
Sevoflurane, a volatile anesthetic, is known to induce widespread neuronal degeneration and apoptosis. Recently, the stress-inducible protein sestrin 2 and adenosine monophosphate-activated protein kinase (AMPK) have been found to regulate the levels of intracellular reactive oxygen species (ROS) and suppress oxidative stress. Notoginsenoside R1 (NGR1), a saponin isolated from , has been shown to exert neuroprotective effects. The effects of NGR1 against neurotoxicity induced by sevoflurane were assessed.
Sprague-Dawley rat pups on postnatal day 7 (PD7) were exposed to sevoflurane (3%) anesthesia for 6 h. NGR1 at doses of 12.5, 25, or 50 mg/kg body weight was orally administered to pups from PD2 to PD7.
Pretreatment with NGR1 attenuated sevoflurane-induced generation of ROS and reduced apoptotic cell counts. Western blotting revealed decreased cleaved caspase 3 and Bad and Bax pro-apoptotic protein expression. NGR1 substantially upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression along with increased heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase-1 levels, suggesting Nrf2 signaling activation. Enhanced sestrin-2 and phosphorylated AMPK expression were noticed following NGR1 pretreatment.
This study revealed the neuroprotective effects of NGR1 through effective suppression of apoptosis and ROS via regulation of apoptotic proteins and activation of Nrf2/HO-1 and sestrin 2/AMPK signaling cascades.
七氟烷是一种挥发性麻醉剂，已知可诱导广泛的神经元变性和凋亡。最近，发现应激诱导蛋白 sestrin 2 和腺苷酸活化蛋白激酶（AMPK）可调节细胞内活性氧（ROS）水平并抑制氧化应激。三七皂苷 R1（NGR1）是从 中分离出的一种皂苷，已显示具有神经保护作用。评估了 NGR1 对七氟烷诱导的神经毒性的影响。
将出生后第 7 天（PD7）的 Sprague-Dawley 大鼠幼崽暴露于 3% 的七氟烷麻醉下 6 小时。从 PD2 到 PD7，以 12.5、25 或 50 mg/kg 体重的剂量给幼崽口服 NGR1。
NGR1 预处理可减轻七氟烷诱导的 ROS 生成并减少凋亡细胞计数。蛋白质免疫印迹显示裂解的半胱天冬酶 3 以及促凋亡蛋白 Bad 和 Bax 的表达降低。NGR1 显著上调核因子红细胞 2 相关因子 2（Nrf2）的表达，同时血红素加氧酶 -1（HO-1）和 NAD(P)H 醌氧化还原酶 -1 水平升高，表明 Nrf2 信号通路被激活。NGR1 预处理后可观察到 sestrin-2 和磷酸化 AMPK 表达增强。
本研究揭示了 NGR1 通过调节凋亡蛋白以及激活 Nrf2/HO-1 和 sestrin 2/AMPK 信号级联反应有效抑制凋亡和 ROS，从而发挥神经保护作用。
