右美托咪定对大鼠海马神经元生长发育的影响及其机制  

Effects of dexmedetomidine on the growth and development of rat hippocampal neurons and its mechanism

作　　者：刘煜鑫 闫东[2] LIU YU-xin;YAN Dong(Department of Anesthesiology, Yongchuan District Children's Hospital, Chongqing 402160;Yongchuan Hospital Affiliated to Medical University of Chongqing, Chongqing 402160, China)

机构地区：[1]重庆永川区儿童医院麻醉科,重庆402160 [2]重庆医科大学附属永川医院麻醉科,重庆402160

出　　处：《中国应用生理学杂志》2019年第1期69-73,共5页Chinese Journal of Applied Physiology

基　　金：重庆市科技计划项目支撑(Ycstc2014nc5003)

摘　　要：目的:探讨右美托咪定(DEX)对新生大鼠海马神经元发育过程及脑源性神经营养因子(BDNF)-酪氨酸受体激酶B(Trk B)信号通路分子表达的影响。方法:从新生的大鼠分离出海马神经元细胞进行体外培养,将细胞接种于96孔板,实验分为4组(对照组、1μmol/L DEX处理组、5μmol/L DEX处理组、50μmol/L DEX处理组),每组设置6复孔,分别给予不同浓度的右美托咪定1、5和50μmol/L处理,于处理后2、4、6、8、10 d检测细胞活性,于处理后10 d检测细胞凋亡情况、q-PCR检测突触素(SYN)和突触后密度蛋白95(PSD95)的mRNA表达水平,分析BDNF、Trk B及N-甲基-D-天冬氨酸受体(NMDA)蛋白表达情况。结果:与对照组相比,不同剂量DEX处理组的神经元细胞活力无显著差异,1μmol/L和5μmol/L DEX处理组中SYN和PSD95 mRNA的表达和Trk B蛋白均无显著性差异(P>0.05),而50μmol/L DEX处理组中SYN和PSD95 mRNA的表达显著升高(P<0.01),BDNF蛋白表达水平显着上调(P<0.01),p-N-甲基-D-天冬氨酸受体的表达增加(P<0.01)。结论:50μmol/L DEX对大鼠海马神经元有一定的作用,其可能通过上调BDNF的表达和N-甲基-D-天冬氨酸受体的磷酸化水平来实现。Objective: To investigate the effects of dexmedetomidine (DEX) on hippocampal neuron development process and the expressions of molecules in brain-derived neurotropic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling pathway in neonatal rats. Methods: The hippocampal neurons were isolated from neonatal rats and cultured in vitro. The cells were seeded in 96-well plates,which were divided into 4 groups (control group, 1 μmol/L DEX treatment group, 5 μmol/L DEX treatment group, 50 μmol/L DEX treatment group), six wells were set in each group, and different concentrations of dexmedetomidine 1, 5 and 50 μmol/L were administered respectively. Cell viability was detected at 2, 4, 6, 8, and 10 d after treatment, and apoptosis was detected 10 days after treatment. The mRNA expression levels of synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) were detected by q-PCR, and the expressions of BDNF, TrkB and N-methyl-D-aspartate receptor (NMDAR) protein were analyzed. Results: Compared with the control group, there was no significant difference in neuronal cell viability between the different doses of DEX treatment group. There was no significant difference in the expression of SYN and PSD95 mRNA and TrkB protein between the 1 μmol/L and 5 μmol/L DEX treatment groups ( P >0.05). The expression levels of SYN and PSD95 mRNA in the 50 μmol/L DEX group were increased significantly ( P <0.01), and the expression level of BDNF protein was up-regulated significantly ( P <0.01), the expression of the p-N-methyl-D-aspartate receptor was increased ( P <0.01). Conclusion: 50 μmol/L DEX has a certain effect on rat hippocampal neurons, which may be achieved by up-regulating the expression of BDNF and the phosphorylation level of N-methyl-D-aspartate receptor.

关 键 词：右美托咪定 海马神经元 脑源性神经营养因子-酪氨酸受体激酶B(BDNF-TrkB) 大鼠 

分 类 号：R338.2[医药卫生—人体生理学]