Greene N D, Copp A J
Neural Development Unit, Institute of Child Health, University of London, UK.
Nat Med. 1997 Jan;3(1):60-6. doi: 10.1038/nm0197-60.
Clinical trials demonstrate that up to 70% of neural tube defects (NTDs) can be prevented by folic acid supplementation in early pregnancy, whereas the remaining NTDs are resistant to folate. Here, we show that a second vitamin, myo-inositol, is capable of significantly reducing the incidence of spinal NTDs in curly tail mice, a genetic model of folate-resistant NTDs. Inositol increases flux through the inositol/lipid cycle, stimulating protein kinase C activity and upregulating expression of retinoic acid receptor beta, specifically in the caudal portion of the embryonic hindgut. This reduces the delay in closure of the posterior neuropore, the embryonic defect that is known to lead directly to spina bifida in curly tail embryos. Our findings reveal a molecular pathway of NTD prevention and suggest the possible efficacy of combined treatment with folate and inositol in overcoming the majority of human NTDs.
临床试验表明，在妊娠早期补充叶酸可预防高达70%的神经管缺陷（NTD），而其余的NTD对叶酸有抗性。在此，我们表明第二种维生素——肌醇，能够显著降低卷尾小鼠（一种叶酸抗性NTD的遗传模型）脊髓NTD的发生率。肌醇增加了通过肌醇/脂质循环的通量，刺激蛋白激酶C活性，并上调视黄酸受体β的表达，特别是在胚胎后肠的尾部。这减少了后神经孔闭合的延迟，而后神经孔是已知直接导致卷尾胚胎脊柱裂的胚胎缺陷。我们的研究结果揭示了NTD预防的分子途径，并表明叶酸和肌醇联合治疗在克服大多数人类NTD方面可能具有疗效。
