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目的:探讨异氟烷对小鼠神经干细胞的BDNF、Caspase3及Notch信号相关基因表达的影响。方法:给予体外培养的新生小鼠海马神经干细胞不同浓度异氟烷处理,实验分为对照组和异氟烷处理组(ISO1.0,ISO1.5),其中异氟烷组细胞分别给予1.0MAC和1.5 MAC两个浓度的异氟烷处理2小时,对照组给予O_2处理2小时,随后置于培养箱正常培养24小时后收集细胞,提取细胞RNA检测BDNF,Caspase3及Notch相关基因(Notch2、Notch 3和Hes5)的m RNA水平变化。结果:与对照组相比,(1)异氟烷组小鼠神经干细胞的功能基因BDNF m RNA水平下调,凋亡相关基因Caspase3的m RNA水平上调;(2)异氟烷组神经干细胞的Notch2和Notch3受体m RNA表达下调,Notch信号通路靶基因Hes5的m RNA水平也明显下调;(3)异氟烷对神经干细胞的作用具有剂量依赖性,浓度越高对神经干细胞BDNF、Caspase3及Notch信号相关基因表达的影响越大。结论:异氟烷可能通过抑制小鼠神经干细胞的Notch信号通路,下调BDNF的m RNA表达,上调Caspase3的m RNA水平,影响神经干细胞的正常功能。
OBJECTIVE: To investigate the effect of isoflurane on the expression of BDNF, Caspase3 and Notch signal-related genes in mouse neural stem cells. Methods: The hippocampal NSCs cultured in vitro were treated with isoflurane in different concentrations. The experiment was divided into control group and isoflurane-treated group (ISO1.0, ISO1.5), in which isoflurane group cells were given 1.0MAC And 1.5 MAC two isoflurane treatment for 2 hours, the control group given O_2 for 2 hours, then placed in the incubator for 24 hours after normal cell collection, cell RNA was extracted to detect BDNF, Caspase3 and Notch related genes (Notch2, Notch 3 and Hes5). Results: Compared with the control group, (1) the BDNF m RNA level of the neural stem cells of isoflurane-treated mice was down-regulated and that of the apoptosis-related gene Caspase3 was up-regulated. (2) Notch2 And m RNA expression of Notch3 receptor were down-regulated. The m RNA level of Hes5, a target gene of Notch signaling pathway, was also significantly down-regulated. (3) The effect of isoflurane on neural stem cells in a dose-dependent manner increased the expression of BDNF, Caspase3 and Notch The greater the impact of signal-related gene expression. CONCLUSION: Isoflurane may affect the normal function of neural stem cells by inhibiting Notch signaling pathway of mouse neural stem cells, down-regulating m RNA expression of BDNF, up-regulating m RNA level of Caspase3.