Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Pudong New Area, Shanghai, 200120, China.
Eur J Drug Metab Pharmacokinet. 2022 Nov;47(6):869-877. doi: 10.1007/s13318-022-00799-0. Epub 2022 Oct 5.
No treatment modalities have been identified to prevent neuron damage induced by traumatic brain injury (TBI). The objective of this study was to investigate whether ginsenoside Rb1 (GS-Rb1) could be utilized to exert neuroprotective effects in TBI.
Lateral fluid percussion injury (LFPI) was used to induce an experimental TBI model. Lewis rats were divided into a GS-Rb1 group (5, 10, 20 mg/kg, intraperitoneally injected daily), a sham group, and a vehicle group. Neurological impairments were assessed with brain water content, Evans blue extravasation, neurological deficit scores, and Morris water maze test. TUNEL and NeuN staining were utilized to detect neuron apoptosis. The relative expression of apoptosis- and autophagy-relevant molecules were assayed with real-time PCR and western blot.
GS-Rb1 inhibited TBI-induced brain edema and Evans blue extravasation in a dose-dependent manner. Furthermore, GS-Rb1 improved neurological impairments with diminished neurological deficit scores, decreased escape latencies, increased time in the target quadrant, and increased number of platform site crossings. GS-Rb1 protected against neuron apoptosis with downregulated Bax expression and upregulated Bcl-2 expression. It was worth noting that TBI increased the LC3II/LC3I ratio and upregulated the relative expression of Beclin-1, Atg-7, and Atg-3; moreover, TBI downregulated the relative expression of P62. The administration of GS-Rb1 further strengthened the relative expression of autophagy-related molecules.
GS-Rb1 alleviates neurological impairments induced by TBI with upregulated autophagy.
目前尚无确定的治疗方法可预防创伤性脑损伤（TBI）引起的神经元损伤。本研究旨在探讨人参皂苷 Rb1（GS-Rb1）是否可用于发挥 TBI 的神经保护作用。
采用侧脑室液压冲击伤（LFPI）制作实验性 TBI 模型。将Lewis 大鼠分为 GS-Rb1 组（5、10、20mg/kg，每日腹腔注射）、假手术组和载体组。采用脑水含量、伊文思蓝渗出、神经功能缺损评分和 Morris 水迷宫试验评估神经损伤。采用 TUNEL 和 NeuN 染色检测神经元凋亡。采用实时 PCR 和 Western blot 检测凋亡和自噬相关分子的相对表达。
GS-Rb1 呈剂量依赖性抑制 TBI 诱导的脑水肿和伊文思蓝渗出。此外，GS-Rb1 改善了神经损伤，表现为神经功能缺损评分降低、逃避潜伏期缩短、目标象限停留时间延长和平台位置穿越次数增加。GS-Rb1 通过下调 Bax 表达和上调 Bcl-2 表达来保护神经元免于凋亡。值得注意的是，TBI 增加了 LC3II/LC3I 比值，并上调了 Beclin-1、Atg-7 和 Atg-3 的相对表达；此外，TBI 下调了 P62 的相对表达。GS-Rb1 的给药进一步增强了自噬相关分子的相对表达。
GS-Rb1 通过上调自噬减轻 TBI 引起的神经损伤。
