多次给药地塞米松对小鼠大脑糖基化成分具有延迟的长期效应

IF 3.2 Q2 CLINICAL NEUROLOGY
Stanislav D Aladev, Dmitry K Sokolov, Anastasia V Strokotova, Galina M Kazanskaya, Alexander M Volkov, Svetlana V Aidagulova, Elvira V Grigorieva
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引用次数: 0

摘要

糖皮质激素用于治疗胶质母细胞瘤,以防止正常脑组织周围的脑水肿效应。我们的研究旨在探讨在体内实验模型中,多次给药糖皮质激素对正常脑细胞外基质糖基化成分(蛋白聚糖和糖胺聚糖)和糖皮质激素受体(GR,Nr3c1)的长期影响。给两个月大的雄性 C57Bl/6 小鼠(n = 90)腹腔注射不同剂量的地塞米松(DXM)(1;2.5 mg/kg),连续 10 天。在第15天、30天、60天和90天时,通过实时RT-PCR测定GR、蛋白多糖核心蛋白和硫酸肝素代谢相关基因的mRNA水平。使用点印迹和阿尔新蓝染色法研究了糖胺聚糖的含量。DXM 处理增加了总 GAG 含量(2 倍),而高度硫酸化的糖胺聚糖含量则减少了(1.5-2 倍)。涉及硫酸肝素代谢的基因 Hs3St2 的 mRNA 水平增加了 5 倍,Hs6St2 的 mRNA 水平增加了 6-7 倍,蛋白聚糖 aggrecan 的 mRNA 水平增加了 2 倍。相关性分析表明,GR 的 mRNA 水平与 14 个编码蛋白多糖的基因中的 8 个基因和 13 个涉及硫酸肝素代谢的基因中的 4 个基因的 mRNA 水平之间存在关联,支持 GR 参与 DXM 对这些基因表达的调控。总之,多次服用 DXM 会导致 GAG 总含量增加,并从糖基化模式的角度重组脑细胞外基质。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Multiple Administration of Dexamethasone Possesses a Deferred Long-Term Effect to Glycosylated Components of Mouse Brain.

Glucocorticoids are used during glioblastoma treatment to prevent the cerebral edema effect surrounding normal brain tissue. The aim of our study was to investigate the long-term effects of multiple administrations of glucocorticoids onto the glycosylated components (proteoglycans and glycosaminoglycans) of normal brain extracellular matrix and the glucocorticoid receptor (GR, Nr3c1) in an experimental model in vivo. Two-month-old male C57Bl/6 mice (n = 90) were injected intraperitoneally with various doses of dexamethasone (DXM) (1; 2.5 mg/kg) for 10 days. The mRNA levels of the GR, proteoglycans core proteins, and heparan sulfate metabolism-involved genes were determined at the 15th, 30th, 60th, and 90th days by a real-time RT-PCR. The glycosaminoglycans content was studied using dot blot and staining with Alcian blue. A DXM treatment increased total GAG content (2-fold), whereas the content of highly sulfated glycosaminoglycans decreased (1.5-2-fold). The mRNA level of the heparan sulfate metabolism-involved gene Hs3St2 increased 5-fold, the mRNA level of Hs6St2 increased6-7-fold, and the mRNA level of proteoglycan aggrecan increased 2-fold. A correlation analysis revealed an association between the mRNA level of the GR and the mRNA level of 8 of the 14 proteoglycans-coding and 4 of the 13 heparan sulfate metabolism-involved genes supporting GR involvement in the DXM regulation of the expression of these genes. In summary, multiple DXM administrations led to an increase in the total GAG content and reorganized the brain extracellular matrix in terms of its glycosylation pattern.

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来源期刊
Neurology International
Neurology International CLINICAL NEUROLOGY-
CiteScore
3.70
自引率
3.30%
发文量
69
审稿时长
11 weeks
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