Aladev Stanislav D, Sokolov Dmitry K, Strokotova Anastasia V, Kazanskaya Galina M, Volkov Alexander M, Aidagulova Svetlana V, Grigorieva Elvira V
Institute of Molecular Biology and Biophysics FRC FTM, Novosibirsk 630117, Russia.
E.N. Meshalkin National Medical Research Center, Novosibirsk 630055, Russia.
Neurol Int. 2024 Jul 22;16(4):790-803. doi: 10.3390/neurolint16040058.
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, ) in an experimental model . 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.
在胶质母细胞瘤治疗期间使用糖皮质激素来预防正常脑组织周围的脑水肿效应。我们研究的目的是在一个实验模型中，研究多次给予糖皮质激素对正常脑细胞外基质的糖基化成分（蛋白聚糖和糖胺聚糖）以及糖皮质激素受体（GR）的长期影响。给2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；2.5mg/kg），持续10天。在第15、30、60和90天通过实时RT-PCR测定GR、蛋白聚糖核心蛋白和硫酸乙酰肝素代谢相关基因的mRNA水平。使用斑点印迹法和阿尔辛蓝染色研究糖胺聚糖含量。DXM治疗使总GAG含量增加（2倍），而高度硫酸化糖胺聚糖的含量降低（1.5 - 2倍）。硫酸乙酰肝素代谢相关基因Hs3St2的mRNA水平增加5倍，Hs6St2的mRNA水平增加6 - 7倍，蛋白聚糖聚集蛋白聚糖的mRNA水平增加2倍。相关性分析显示，GR的mRNA水平与14个蛋白聚糖编码基因中的8个以及13个硫酸乙酰肝素代谢相关基因中的4个的mRNA水平之间存在关联，支持GR参与DXM对这些基因表达的调节。总之，多次给予DXM导致总GAG含量增加，并使其脑细胞外基质的糖基化模式发生重组。
