异氟醚麻醉抑制海马齿状回神经干细胞的增殖及分化

Isoflurane inhibits proliferation and differentiation of neural stem cells in the dentate gyrus

背景:异氟醚由于起效快、苏醒迅速、无积蓄等优点在儿科手术也逐渐被推广使用,然而其安全性还需要进一步观察。目的:观察异氟醚麻醉对新生大鼠海马齿状回神经干细胞增殖及神经元分化的影响。方法:将大鼠随机分为异氟醚组和对照组,分别予以异氟醚吸入麻醉和仅吸入空气。分别在给药前及停止给约后对动物予以5-溴脱氧球苷(Brd U)腹腔注射,第2次注射后24 h处死大鼠,获得脑组织,检测Brd U+和脑内神经源性分化因子表达情况。结果与结论:停止麻醉处理之后进行血糖以及动脉血气检测,发现异氟醚组大鼠Pa CO2出现轻度上升,p H值出现轻微下降,而Pa O2、BE、Sa O2以及血糖水平则均未出现改变。与对照组相比,异氟醚组经异氟醚麻醉之后,未出现明显的缺氧表现,包括紫绀和呼吸抑制等。大鼠海马齿状回神经干细胞大多分布在门区,异氟醚组的Brd U阳性细胞数少于对照组(P<0.05)。两组大鼠海马齿状回存在大量新生细胞表达Neuro D,门区Neuro D+/Brd U+阳性细胞数明显高于颗粒细胞下区,且异氟醚组显著高于对照组(P<0.05)。结果证实,异氟醚麻醉会对新生大鼠海马齿状回神经干细胞增殖及神经元分化产生一定的影响,抑制其增殖,并促进其神经元分化。

BACKGROUND： Isoflurane is gradually popularized in pediatric surgery due to its rapid onset, rapid recovery, and no savings, but its security needs to be further studied. OBJECTIVE： To explore the effect of isoflurane anesthesia on the proliferation and neuronal differentiation of neural stem cells in the dentate gyrus of neonatal rats. METHODS： Rats were randomly divided into isoflurane group and control group, respectively treated with isoflurane inhalation and air inhalation. 5-Bromodeoxyundine ball glycosides （BrdU） was intraperitoneally injected before drug administration and after drug withdrawal, and 24 hours after secondary injection, the rats were executed to take brain tissues for detection of BrdU expression and brain neurogenic differentiation factor expression. RESULTS AND CONCLUSION： After cessation of anaesthesia processing for the detection of blood glucose and arterial blood gas, a mild rise in PaCO2 was found in the isoflurane group and pH showed a slight drop, but PaO2, BE, SaO2 and blood glucose levels were not changed. Compared with the control group, the isoflurane group did not appear with obvious hypoxia performances after isoflurane anesthesia, including cyanosis and respiratory depression. Rat neural stem cells of the dentate gyrus were mostly distributed in the gate area, and compared with the control group, the number of BrdU-positive cells was less in the isoflurane group （P 〈 0105）. A large number of new cells in the dentate gyrus expressed NeuroD, and the number of NeuroD＋/BrdU＋ cells in the gate area was significantly higher than that in the lower region of granule cells. Moreover, the number ofNeuroD＋/BrdU＋ cells in the isoflurane group was significantly higher than that in the control group （P 〈 0.05）. These findings suggest that isoflurane anesthesia can influence the proliferation and neuronal differentiation of neural stem cells in the dentate gyrus of neonatal rats, which inhibits cell proliferation and promotes neuronal differentiation.