产前补充牛磺酸调节Rho家族因子活性促进生长受限新生大鼠神经干细胞增殖的研究

Effect of antepartum taurine supplementation in regulating the activity of Rho family factors and promoting the proliferation of neural stem cells in neonatal rats with fetal growth restriction

摘要:

目的 探讨产前补充牛磺酸通过调节Rho家族因子活性促进生长受限 （FGR）新生大鼠神经干细胞增殖的可能性，为产前补充牛磺酸促进生长受限患儿脑发育提供实验依据。方法 将24只Sprague-Dawley孕鼠随机分为对照组、FGR组、牛磺酸组 （n=8），通过全程饥饿法建立FGR模型。采用逆转录-聚合酶链反应法、免疫组化及免疫印迹法检测各组新生鼠脑组织神经干细胞特异性胞内标记物脂肪酸结合蛋白7 （FABP7）、Rho相关螺旋卷曲蛋白激酶2 （ROCK2）、ras同源基因家族成员A （RhoA）、Ras相关的C3肉毒素底物 （rac）表达水平。结果 FGR组FABP7阳性细胞OD值、FABP7mRNA及蛋白的表达低于对照组，牛磺酸组FABP7阳性细胞OD值、FABP7mRNA及蛋白的表达高于FGR组 （P < 0.05）。FGR组中RhoA、ROCK2mRNA的表达高于对照组，牛磺酸组中RhoA、ROCK2mRNA表达高于对照组但低于FGR组 （P < 0.05）；FGR组中racmRNA的表达低于对照组，牛磺酸组中racmRNA表达高于FGR组及对照组 （P < 0.05）；FGR组中RhoA、ROCK2蛋白表达水平高于对照组，牛磺酸组中RhoA、ROCK2蛋白表达水平低于FGR组 （P < 0.05）。结论 产前补充牛磺酸可促进FGR新生大鼠神经干细胞增殖，其机制可能与调控Rho家族因子的活性有关。

Abstract:

Objective To study the possible effect of antepartum taurine supplementation in regulating the activity of Rho family factors and promoting the proliferation of neural stem cells in neonatal rats with fetal growth restriction (FGR), and to provide a basis for antepartum taurine supplementation to promote brain development in children with FGR. Methods A total of 24 pregnant Sprague-Dawley rats were randomly divided into three groups:control, FGR, and taurine (n=8 each). A rat model of FGR was established by food restriction throughout pregnancy. RT-PCR, immunohistochemistry, and Western blot were used to measure the expression of the specific intracellular markers for neural stem cells fatty acid binding protein 7 (FABP7), Rho-associated coiled-coil containing protein kinase 2 (ROCK2), ras homolog gene family, member A (RhoA), and Ras-related C3 botulinum toxin substrate (Rac). Results The FGR group had significantly lower OD value of FABP7-positive cells and mRNA and protein expression of FABP7 than the control group, and the taurine group had significantly higher OD value of FABP7-positive cells and mRNA and protein expression of FABP7 than the FGR group (P < 0.05). The FGR group had significantly higher mRNA expression of RhoA and ROCK2 than the control group. The taurine group had significantly higher mRNA expression of RhoA and ROCK2 than the control group and significantly lower expression than the FGR group (P < 0.05). The FGR group had significantly lower mRNA expression of Rac than the control group. The taurine group had significantly higher mRNA expression of Rac than the FGR and control groups (P < 0.05). The FGR group had significantly higher protein expression of RhoA and ROCK2 than the control group. The taurine group had significantly lower protein expression of RhoA and ROCK2 than the FGR group (P < 0.05). Conclusions Antepartum taurine supplementation can promote the proliferation of neural stem cells in rats with FGR, and its mechanism may be related to the regulation of the activity of Rho family factors.