丙戊酸 (Valproic Acid)對於脊髓損傷大鼠之影響

前言：外傷性脊髓損傷 (Traumatic Spinal Cord Injury, SCI)所引發初期發炎反應會造成神經元受損、細胞型態變異、細胞凋亡，並誘發相關蛋白質量的增減。Valproic acid (VPA)為目前廣泛用於治療癲癇的藥物，已有研究顯示VPA為組織蛋白去乙醯化酶的抑制劑，並可調控基因的表現調節轉錄作用，且組織蛋白的乙醯化作用為細胞發炎以及修復過程的關鍵。方法：本實驗分成兩部份，第一部份為低劑量組 (30mg/kg,7d)並隨機分成四組—假手術組、假手術給予VPA治療組、脊髓損傷組、VPA治療組；第二部份為單一劑量組 (30mg/kg、100mg/kg、200mg/kg,24hr)分組方式與第一部份相同。使用Basso, Beattie and Bresnahan (BBB)評分表衡量四組大鼠的行為運動功能，利用免疫螢光染色探討神經元形態及細胞凋亡的情形以及西方墨點法下各蛋白質的表現量。結果： VPA會促進脊髓損傷後神經元的修復，降低細胞凋亡的發生，增加神經突觸的生長，並且有益於損傷後大鼠的行為運動功能。

關鍵字

脊髓損傷； Valproic acid ；細胞凋亡；神經元

並列摘要

Introduction－In initial inflammatory reactions induced by Traumatic Spinal Cord Injury (SCI) causes damages to neurons, morphological changes at the cellular level, apoptosis, and a decrease in the expression of pertinent proteins. Valproic acid, a commonly used epilepsy treatment, has been shown to inhibit the deacetylation of histones, which is a critical step in the inflammatory and repair processes. In addition, VPA is also implicated in the modulation of gene expression. Method－This experiment consists of 2 parts. Part 1 is the low dosage group, which is subdivided into 4 groups randomly: sham, sham+VPA, SCI, and SCI+VPA. Part 2 is the single dosage group, which is subdivided into 4 groups in the same manner as group 1. The Basso, Beattie and Bresnahan (BBB) scoring method was then applied to analyze the locomotion of rats. Immunoflurecence was applied to analyze the morphological changes in neurons and apoptosis. Furthermore, western blot was used to quantify the expression of proteins. Result－VPA promoted the healing of neurons and the growth of axons after SCI. In addition, it also caused a decrease in apoptosis, and improved in the locomotion of rats.

並列關鍵字

spianl cord injury ； Valproic acid ； apoptosis ； neuron

參考文獻

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丙戊酸 (Valproic Acid)對於脊髓損傷大鼠之影響

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