Chen Dingzhi, Xie Jieqiong, Chen Xueyuan, Qin Biyun, Kong Deyan, Luo Jiefeng
Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China.
Neuroscience. 2025 Jan 9;564:299-305. doi: 10.1016/j.neuroscience.2024.10.053. Epub 2024 Nov 2.
This study aims to delve into the mechanisms underlying the improvement of neurological function in rats with ischemic stroke through fecal microbiota transplantation.
A total of fifty male Sprague-Dawley rats were categorized into four groups: Sham, MCAO, MCAO+vehicle and FMT. We assessed behavioral and pathological alterations in the rats using modified neurological function scoring and TTC staining.Additionally, Western blot and immunofluorescence were used to detect the expression levels of Apoptotic and Necroptosis markers in neurons of ischemic brain tissue, and immunofluorescence was used to analyze the degree of activation of microglia.
FMT group exhibited a decline in neurological function score compared to the MCAO and MCAO + vehicle group, accompanied by a reduction in infarct volume (P < 0.05). Relative to the SHAM group, the MCAO group displayed a significant increase in the expression levels of necroptosis-related proteins Phospho-RIP1, Phospho-RIP3, Phospho-MLKL, apoptotic proteins Bax and Cleaved caspase-3, and the iNOS positive microglia in ischemic brain tissue, while Bcl-2 expression was notably decreased (P < 0.05).Conversely, compared to the MCAO + vehicle group, the FMT group showed decreased expression levels of Phospho-RIP1, Phospho-RIP3, Phospho-MLKL, Bax, Cleaved caspase-3, and iNOS-positive microglia, while the expression of Bcl-2 was increased.
Fecal microbiota transplantation offers a promising approach to improving neurological function in rats with ischemic stroke by inhibiting neuronal apoptosis, necroptosis, and the polarization of inflammatory microglial cells.
本研究旨在探究通过粪便微生物群移植改善缺血性脑卒中大鼠神经功能的潜在机制。
将总共50只雄性Sprague-Dawley大鼠分为四组：假手术组、大脑中动脉闭塞（MCAO）组、MCAO+载体组和粪便微生物群移植（FMT）组。我们使用改良的神经功能评分和TTC染色评估大鼠的行为和病理变化。此外，采用蛋白质免疫印迹法和免疫荧光法检测缺血脑组织神经元中凋亡和坏死性凋亡标志物的表达水平，并用免疫荧光法分析小胶质细胞的激活程度。
与MCAO组和MCAO+载体组相比，FMT组神经功能评分下降，梗死体积减小（P<0.05）。相对于假手术组，MCAO组缺血脑组织中坏死性凋亡相关蛋白磷酸化RIP1、磷酸化RIP3、磷酸化混合谱系激酶结构域样蛋白（Phospho-MLKL）、凋亡蛋白Bax和裂解的半胱天冬酶-3以及诱导型一氧化氮合酶（iNOS）阳性小胶质细胞的表达水平显著升高，而Bcl-2表达明显降低（P<0.05）。相反，与MCAO+载体组相比，FMT组磷酸化RIP1、磷酸化RIP3、磷酸化MLKL、Bax、裂解的半胱天冬酶-3和iNOS阳性小胶质细胞的表达水平降低，而Bcl-2表达增加。
粪便微生物群移植通过抑制神经元凋亡、坏死性凋亡和炎性小胶质细胞极化，为改善缺血性脑卒中大鼠的神经功能提供了一种有前景的方法。
