College of Medical Technology, Qiqihar Medical University, No.333 Bukui Street, Jianhua District, Qiqihar, Heilongjiang 161006, China.
Department of Radiotherapy, The Third Affiliated Hospital of Qiqihar Medical University, No.27, Taishun Street, Tiefeng District, Qiqihar, Heilongjiang 161006, China.
Brain Res. 2024 Apr 15;1829:148795. doi: 10.1016/j.brainres.2024.148795. Epub 2024 Feb 7.
Bone marrow mesenchymal stem cell (BMSCs) -based therapies represent a promising treatment for neurological disorders. However, therapeutic effects and mechanisms of BMSCs transplantation for radiation-induced brain injury (RIBI) have not been fully disclosed. In this article, we explored the functions of BMSCs transplantation on RIBI and investigated the protective effects of BMSCS on hippocampal neurons in RIBI as well as the related molecular mechanisms.
6-8 weeks-old rats were used to build a RIBI model. Rats in BMSC group were treated with a 3 × 10 BMSCs injection through the tail vein on the 1st day and 8th day after irradiation; rats in both control and RIBI groups were injected with an equivalent volume of physiological saline for comparisons. The Morris water maze was applied to detect the variations in cognitive function after RIBI. MRS was performed to test changes in NAA/Cr, indicating neuronal apoptosis after RIBI. TUNEL was conducted to detect apoptosis of rat hippocampal neurons, and HE staining was carried out to show pathological variations in the hippocampal region of rats. Protein levels of PI3K, P-PI3K, AKT, P-AKT, Bcl-2, and Bax proteins of rats in the hippocampal area were all determined by Western blot.
Cognitive function was reduced and hippocampal neurons underwent apoptosis in the rats of the RIBI group, and cognitive abilities, histopathological alterations, and apoptosis of hippocampal neurons were significantly improved after BMSCs treatment; the expression of PI3K, P-PI3K, AKT, P-AKT, and Bcl-2 proteins, in the hippocampal region of the rat, was up-regulated, and Bax proteins were down-regulated.
BMCSs can inhibit hippocampal neuronal apoptosis in RIBI, and the mechanism may be associated with the up-regulation of Bcl-2 and down-regulation of Bax by the PI3K/AKT signaling pathway.
骨髓间充质干细胞（BMSCs）治疗为神经退行性疾病提供了一种很有前途的治疗方法。然而，BMSCs 移植治疗放射性脑损伤（RIBI）的疗效和机制尚未完全阐明。本文旨在探讨 BMSCs 移植对 RIBI 的作用，并研究 BMSCs 对 RIBI 中海马神经元的保护作用及其相关分子机制。
采用 6-8 周龄大鼠建立 RIBI 模型。在照射后第 1 天和第 8 天，BMSC 组大鼠通过尾静脉注射 3×10 BMSCs；对照组和 RIBI 组大鼠分别注射等量生理盐水作为对照。采用 Morris 水迷宫检测 RIBI 后大鼠认知功能的变化。MRS 检测 NAA/Cr 的变化，反映神经元凋亡。TUNEL 检测大鼠海马神经元凋亡，HE 染色观察大鼠海马区病理变化。Western blot 检测大鼠海马区 PI3K、P-PI3K、AKT、P-AKT、Bcl-2 和 Bax 蛋白的表达。
RIBI 组大鼠认知功能下降，海马神经元凋亡，BMSCs 治疗后大鼠认知能力、海马组织病理改变和神经元凋亡明显改善；大鼠海马区 PI3K、P-PI3K、AKT、P-AKT 和 Bcl-2 蛋白表达上调，Bax 蛋白表达下调。
BMSCs 可抑制 RIBI 中海马神经元凋亡，其机制可能与 PI3K/AKT 信号通路上调 Bcl-2 和下调 Bax 有关。
