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丙戊酸可增加脊髓损伤中神经干细胞/祖细胞的表达。

Valproic Acid increases expression of neuronal stem/progenitor cell in spinal cord injury.

作者信息

Bang Woo-Seok, Kim Kyoung-Tae, Cho Dae-Chul, Kim Hye-Jeong, Sung Joo-Kyung

机构信息

Department of Neurosurgery, Kyungpook National University Hospital, Daegu, Korea.

出版信息

J Korean Neurosurg Soc. 2013 Jul;54(1):8-13. doi: 10.3340/jkns.2013.54.1.8. Epub 2013 Jul 31.

DOI:10.3340/jkns.2013.54.1.8
PMID:24044073
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3772294/
Abstract

OBJECTIVE

This study investigates the effect of valproic acid (VPA) on expression of neural stem/progenitor cells (NSPCs) in a rat spinal cord injury (SCI) model.

METHODS

Adult male rats (n=24) were randomly and blindly allocated into three groups. Laminectomy at T9 was performed in all three groups. In group 1 (sham), only laminectomy was performed. In group 2 (SCI-VPA), the animals received a dose of 200 mg/kg of VPA. In group 3 (SCI-saline), animals received 1.0 mL of the saline vehicle solution. A modified aneurysm clip with a closing force of 30 grams was applied extradurally around the spinal cord at T9, and then rapidly released with cord compression persisting for 2 minutes. The rats were sacrificed and the spinal cord were collected one week after SCI. Immunohistochemistry (IHC) and western blotting sample were obtained from 5 mm rostral region to the lesion and prepared. We analyzed the nestin immunoreactivity from the white matter of ventral cord and the ependyma of central canal. Nestin and SOX2 were used for markers for NSPCs and analyzed by IHC and western blotting, respectively.

RESULTS

Nestin and SOX2 were expressed significantly in the SCI groups but not in the sham group. Comparing SCI groups, nestin and SOX2 expression were much stronger in SCI-VPA group than in SCI-saline group.

CONCLUSION

Nestin and SOX2 as markers for NSPCs showed increased expression in SCI-VPA group in comparison with SCI-saline group. This result suggests VPA increases expression of spinal NSPCs in SCI.

摘要

目的

本研究在大鼠脊髓损伤（SCI）模型中探讨丙戊酸（VPA）对神经干/祖细胞（NSPCs）表达的影响。

方法

将24只成年雄性大鼠随机、盲法分为三组。三组均行T9椎板切除术。第1组（假手术组）仅行椎板切除术。第2组（SCI-VPA组）动物接受200mg/kg的VPA剂量。第3组（SCI-生理盐水组）动物接受1.0mL生理盐水载体溶液。使用一个闭合力为30克的改良动脉瘤夹在T9脊髓硬膜外环绕脊髓，然后迅速释放，使脊髓压迫持续2分钟。脊髓损伤一周后处死大鼠并收集脊髓。从损伤部位头侧5mm处获取免疫组织化学（IHC）和蛋白质印迹样本并制备。我们分析了脊髓腹侧白质和中央管室管膜的巢蛋白免疫反应性。分别使用巢蛋白和SOX2作为NSPCs的标志物，通过免疫组织化学和蛋白质印迹进行分析。

结果

巢蛋白和SOX2在脊髓损伤组中显著表达，但在假手术组中未表达。比较脊髓损伤组，SCI-VPA组中巢蛋白和SOX2的表达比SCI-生理盐水组强得多。

结论

与SCI-生理盐水组相比，作为NSPCs标志物的巢蛋白和SOX2在SCI-VPA组中表达增加。这一结果表明VPA可增加脊髓损伤中脊髓NSPCs的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f07/3772294/111a10f0ae20/jkns-54-8-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f07/3772294/4b91fab4a501/jkns-54-8-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f07/3772294/b492454998bc/jkns-54-8-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f07/3772294/22ff5cc49d89/jkns-54-8-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f07/3772294/490550833104/jkns-54-8-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f07/3772294/7ec15033b03e/jkns-54-8-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f07/3772294/111a10f0ae20/jkns-54-8-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f07/3772294/4b91fab4a501/jkns-54-8-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f07/3772294/b492454998bc/jkns-54-8-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f07/3772294/22ff5cc49d89/jkns-54-8-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f07/3772294/490550833104/jkns-54-8-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f07/3772294/7ec15033b03e/jkns-54-8-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f07/3772294/111a10f0ae20/jkns-54-8-g006.jpg

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Prenatal exposure to valproic acid increases the neural progenitor cell pool and induces macrocephaly in rat brain via a mechanism involving the GSK-3β/β-catenin pathway.产前暴露于丙戊酸通过涉及 GSK-3β/β-连环蛋白途径的机制增加大鼠脑内神经祖细胞池并诱导大头畸形。
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Valproic acid prevents penile fibrosis and erectile dysfunction in cavernous nerve-injured rats.丙戊酸可预防海绵体神经损伤大鼠的阴茎纤维化和勃起功能障碍。
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The neuroprotective effect of treatment of valproic Acid in acute spinal cord injury.
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