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石杉碱甲加重 D-半乳糖诱导的大鼠神经退行性变模型的神经化学和容积改变。

Huperzine aggravated neurochemical and volumetric changes induced by D-galactose in the model of neurodegeneration in rats.

机构信息

Central Laboratories, Faculty of Chemical and Food Technology, Slovak University of Technology, Bratislava, Slovakia; Department of Radiology, Faculty of Medicine of Comenius University in Bratislava, Slovak Medical University and University Hospital Bratislava, Bratislava, Slovakia.

Central Laboratories, Faculty of Chemical and Food Technology, Slovak University of Technology, Bratislava, Slovakia; Department of Radiology, Faculty of Medicine of Comenius University in Bratislava, Slovak Medical University and University Hospital Bratislava, Bratislava, Slovakia.

出版信息

Neurochem Int. 2022 Sep;158:105365. doi: 10.1016/j.neuint.2022.105365. Epub 2022 May 28.

DOI:10.1016/j.neuint.2022.105365
PMID:35636645
Abstract

The multimodal MRI and H MRS study was designed to provide a structural and neurochemical view of D-galactose induced rat brain degeneration and its treatment with huperzine A. The volume changes were captured using MRI focused on the hippocampal region and a neurochemical profile was obtained from the same area using in vivo localized H MRS, which was compared with in vitroH MRS hippocampal spectra at the high field after the animals were culled. At the four week point, we observed a small decrease in N-acetylaspartate/creatine (NAA/tCr), myo-inositol/creatine (mIns/tCr) and glutamine/creatine (Gln/tCr) in the group in which neurodegeneration was induced. At the eight week point, we found only slight but statistically significant decreases in NAA/tCr, mIns/tCr and glutamate/creatine (Glu/tCr) in this group in vivo. However, in the treated group, the decrease in NAA/tCr and Glu/tCr was much more pronounced compared to the D-gal group. In vitroH MRS analysis from rat hippocampal samples showed very similar changes in metabolites, which were also much more pronounced in the treated group. Neurodegeneration was also confirmed by a significant decrease in γ-aminobutyrate/creatine (GABA/tCr) observed only in the treated group, but not in the D-gal group. MRI image data and subsequent volumetric quantification showed mild hippocampal degeneration at the four week point in D-gal group. At the eight week point, we observed a decrease in hippocampal volume in both experimental groups, with a more pronounced decrease in the huperzine-treated group. In conclusion, in our experimental design huperzine A treatment worsened the neurodegeneration of the rat brain, which was supported by all of the used MRI and H MRS methods.

摘要

多模态 MRI 和 H MRS 研究旨在提供 D-半乳糖诱导的大鼠脑退行性变及其用石杉碱甲治疗的结构和神经化学视图。使用聚焦于海马区的 MRI 捕获体积变化,并使用来自同一区域的体内局部 H MRS 获得神经化学谱,然后将其与动物被宰杀后在高场进行的体外 H MRS 海马谱进行比较。在四周时,我们观察到诱导神经退行性变的组中 N-乙酰天冬氨酸/肌酸(NAA/tCr)、肌醇/肌酸(mIns/tCr)和谷氨酰胺/肌酸(Gln/tCr)略有下降。在八周时,我们发现仅在该组体内观察到 NAA/tCr、mIns/tCr 和谷氨酸/肌酸(Glu/tCr)的轻微但具有统计学意义的下降。然而,在治疗组中,与 D-半乳糖组相比,NAA/tCr 和 Glu/tCr 的下降更为明显。来自大鼠海马样本的体外 H MRS 分析显示代谢物也发生了非常相似的变化,在治疗组中变化更为明显。仅在治疗组中观察到 γ-氨基丁酸/肌酸(GABA/tCr)的显著下降证实了神经退行性变,但在 D-半乳糖组中则没有。MRI 图像数据和随后的体积定量显示 D-半乳糖组在四周时出现轻度海马退行性变。在八周时,我们观察到两个实验组的海马体积均减少,在石杉碱甲治疗组中减少更为明显。总之,在我们的实验设计中,石杉碱甲治疗加重了大鼠脑的神经退行性变,所有使用的 MRI 和 H MRS 方法都支持这一结果。

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