中国临床药理学杂志2017，Vol.33Issue(8)：714-717,4.DOI:10.13699/j.cnki.1001-6821.2017.08.012
丙戊酸联合骨髓间充质干细胞移植对大鼠脊髓损伤的影响
Effect of valproate combined with bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats
摘要
Abstract
Objective To investigate the effects of intraperitoneal injection of valproic acid (VPA) combined with transplantation of bone marrow mesenchymal stem cells (BMSCs) on neurological function recovery after spinal cord injury (SCI) in rats.Methods BMSCs from 3-4 weeks old healthy male Sprague-Dawley (SD) rats were cultured in vitro.The third generation BMSCs were detected by flow cytometry.Spinal cord injury model was made by modified Allen's technique.Sixty adult male SD rats were randomly divided into five groups(n =12 in each group):Sham operation group and model group(received the same dose of normal saline at the same time point),VPA group(VPA,one time per q12 h with 300 mg· kg-1 · d-1).BMSCs group (1 × 106 cell· mL-1BMSCs 1 mL injected into the spinal cord of injured segment)and combined group(VPA + BMSCs).The BBB scale at the 14 d after injury was evaluated.The expression of Caspase-3 protein was detected by immunohistochemistry.Then the neuronal apoptosis rate was observed by TdT-mediated dUTP nick-end labeling(TUNEL) staining.Results BBB Rating:On the 14 d after SCI,the rate in sham operation group,model group,VPA group,BMSCs group and combined group were 21,(4.51 ± 0.41),(7.25 ± 0.95),(7.32 ± 0.55),(9.76 ± 0.95)point.The BBB score of the three treatment groups was significantly higher than that of model group with significantly (P ＜ 0.05).On the 14 d after SCI,the caspase-3 expression in sham operation group,model group,VPA group and BMSCs group and combined group were (1.64 ± 0.41) ％,(26.22 ± 4.81) ％,(21.21 ± 4.04) ％,(21.47 ± 3.32) ％,(16.15 ± 3.09) ％.The expression of Caspase-3 in three treatment groups was significantly lower than that model group with significantly(P ＜0.05).While the expression of caspase-3 in combined group was significantly lower than that in VPA group and BMSCs group with significantly(P ＜0.05).On the 14 d after SCI,the apoptosis rate in sham operation group,model group,VPA group and BMSCs group and combined group were (4.18 ± 0.39)％,(40.51 ± 3.81)％,(19.95 ± 2.04)％,(20.87 ±2.32)％,(12.83 ± 1.09)％.Compared with model group,the apoptosis rate of the three treatment groups was lower with significantly(P ＜ 0.05).The apoptosis rate of combined group was significantly lower than that of VPA group and BMSCs group with significantly (P ＜ 0.05).Conclusion It is very significant effects of intraperitoneal injection of VPA combined with BMSCs on neurological function recovery after spinal cord injury in rats.The mechanism may be related to down-regulation of Caspase-3 expression,leading to inhibition of apoptosis.关键词
丙戊酸/骨髓间充质于细胞/脊髓损伤/细胞凋亡/半胱氨酸天冬氨酸蛋白酶3Key words
valproic acid/bone marrow mesenchymal stem cells/spinal cord injury/cell apoptosis/Caspase-3分类
医药卫生引用本文复制引用
张振梁,杨新明,孟宪勇,胡长波,成垚昱,康聪..丙戊酸联合骨髓间充质干细胞移植对大鼠脊髓损伤的影响[J].中国临床药理学杂志,2017,33(8):714-717,4.基金项目
河北省卫生厅医学科学研究重点项目计划基金资助项目(20110176) （20110176）
河北北方学院创新人才培育基金资助项目(2013-CXRC1322) （2013-CXRC1322）
