孕鼠补充牛磺酸促进生长受限胎鼠神经干细胞增殖分化及机制研究

Every year, nearly 2 million infants are born with fetal growth restriction (FGR) in China. FGR is one of the major causes of cerebral palsy and severe disabilities of the nervous system. Taurine，an essential amino acid ,had found wide use in promoting the growth and development of fetus and neonate. Our previous studies have confirmed that antenatal taurine supplementation can boost the neuron proliferation of fetal rats with FGR through regulating cAMP-PKA-CREB and Rho-ROCK signal pathway.However,its specific mechanism whether taurine could improve fetal brain development by promoting the proliferation and differentiation of neural stem cells (NSC) or not still remains unclear.Recent studies have confirmed that cAMP-PKA-CREB and Rho-ROCK systems are critical signal pathways of NSC proliferation and differentiation.Therefore,this study is to confirm whether antenatal taurine supplementation could promote the proliferation and differentiation of NSC and its possible mechanism by:(1) establishing of the FGR fetal rat model and culturing NSC in vitro;(2) blocking these two signal pathways；（3）observing the changes of proliferation and differentiation of NSC in the subventricular zone and cerebral cortex, and the expression changes of key signal molecules in these two signal pathways using qRT-PCR,immunohistochemistry and western blot.The results of this study is expected to provide theoretical insights for antenatal taurine improving FGR fetal brain development.

我国每年有近200万宫内生长受限（FGR）胎儿出生，FGR是造成脑瘫和严重神经系统伤残的重要原因之一。牛磺酸是胎儿神经系统发育的必需氨基酸，本课题组前期研究证实孕鼠牛磺酸可通过调节cAMP-PKA-CREB与Rho-ROCK信号通路的活性而促进FGR胎鼠神经元增殖。由于这两条信号通路也是调节神经干细胞（NSC）增殖分化的重要途径，故我们推测牛磺酸也可通过调节它们的活性而促进NSC增殖与分化。为此，本研究拟通过建立SD大鼠FGR模型，通过整体动物模型与体外NSC原代培养和传代，结合使用阻断剂阻断两条通路，采用qRT-PCR、免疫组化、Western blot等技术，观察孕鼠补充牛磺酸后FGR胎鼠室管膜下生发基质区及大脑皮层NSC增殖、分化及两条信号通路中关键信号分子表达的变化，研究牛磺酸促进FGR胎鼠NSC增殖与分化的可能性及其机制，为产前补充牛磺酸促进FGR胎儿脑发育提供新的理论依据。

宫内生长受限是孕期临床常见疑难问题，由于孕母受到宫内不良因素、尤其蛋白质营养不良的影响，使胎儿在宫内生长发育迟滞。近年研究发现宫内生长受限严重影响胎儿脑发育，是出生后脑瘫的第一位独立高危因素，其脑瘫发生率是适于胎龄儿的6-8倍，但出生后的干预往往难以达到理想效果，故加强产前干预意义重大。.牛磺酸是胎儿新生儿脑生长发育的必须氨基酸，生长受限胎鼠存在脑组织牛磺酸水平低下，而给孕鼠补充牛磺酸可以促进生长受限胎鼠神经元增值，从而促进其脑发育。.本研究进一步证实，孕鼠补充牛磺酸可以促进生长受限胎鼠神经干细胞增殖及分化，为产前补充牛磺酸促进生长受限胎鼠脑发育提供了进一步的理论支持。.牛磺酸无毒无害，是胎儿新生儿生在发育必需氨基酸，因此，本研究成果可以直接应用于临床。