Lv Jie, Ou Wei, Zou Xiao-Hua, Yao Yin, Wu Jin-Li
Department of Anesthesia, Guizhou Medical University Affiliated Hospital, Guiyang, People's Republic of China.
Neuropsychiatr Dis Treat. 2016 Dec 9;12:3153-3159. doi: 10.2147/NDT.S120078. eCollection 2016.
The study aimed to explore the effect of dexmedetomidine (DEX) on hippocampal neuron development process and on molecular expression of brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling pathway in neonatal rats. The hippocampal neuron cells were isolated from newborn neonatal rats and cultured in vitro. One control group and three treated groups with 1, 10, and 100 μmol/L DEX were used for the study. Cell activity and apoptosis were detected by the MTT and terminal deoxynucleotidyl transferase-mediated biotinylated uridine triphosphate (UTP) nick end labeling assays. The synaptophysin (SYN) and postsynaptic density 95 (PSD95) were detected by quantitative polymerase chain reaction. There was no difference in the viability of neuron cells among the different dose groups of DEX and the control group during days 2-10 (>0.05). Compared to the control group, there was no significant difference (>0.05) in the expressions of SYN and PSD95 in the groups treated with 1 and 10 μmol/L DEX, whereas significant difference in the expression was observed in the group treated with 100 μmol/L DEX (<0.01). Compared with the control group, the expression of BDNF was significantly upregulated (<0.05) in the group treated with 100 μmol/L DEX. There were no significant differences in TrkB expression among the four groups. The expression of p-N-methyl-D-aspartate receptor increased with an increase in the concentration of DEX; however, only the high dose revealed a significant upregulation compared with the control group. The neuroprotective effect of DEX may be achieved by upregulating the expression of BDNF and phosphorylation level of N-methyl-D-aspartate receptor.
该研究旨在探讨右美托咪定（DEX）对新生大鼠海马神经元发育过程以及脑源性神经营养因子（BDNF）-酪氨酸受体激酶B（TrkB）信号通路分子表达的影响。从新生大鼠中分离出海马神经元细胞并进行体外培养。实验设一个对照组和三个分别用1、10和100 μmol/L DEX处理的组。通过MTT法和末端脱氧核苷酸转移酶介导的生物素化尿苷三磷酸（UTP）缺口末端标记法检测细胞活性和凋亡情况。通过定量聚合酶链反应检测突触素（SYN）和突触后致密蛋白95（PSD95）。在第2至10天，DEX不同剂量组与对照组之间神经元细胞活力无差异（>0.05）。与对照组相比，1和10 μmol/L DEX处理组的SYN和PSD95表达无显著差异（>0.05），而100 μmol/L DEX处理组的表达有显著差异（<0.01）。与对照组相比，100 μmol/L DEX处理组的BDNF表达显著上调（<0.05）。四组之间TrkB表达无显著差异。p-N-甲基-D-天冬氨酸受体的表达随DEX浓度增加而增加；然而，只有高剂量组与对照组相比有显著上调。DEX的神经保护作用可能是通过上调BDNF的表达和N-甲基-D-天冬氨酸受体的磷酸化水平来实现的。
