杜克大学医学中心(Duke University Medical Center)的研究人员发现,胆固醇也许可以预防胎儿酒精症候群(Fetal Alcohol Syndrome,以下简称FAS)。此研究发表于3月份的Laboratory Investigation期刊。研究经费由NIH(National Institutes of Health)及AHA(American Heart Association)资助。
胆固醇对胎儿的发育扮演相当重要的角色,怀孕妇女即使滴酒不沾,若其胆固醇量不足也会造成胎儿发育上的许多问题。Yin-Xiong Li博士说:「即使很少量的酒精,都会阻扰胚胎中细胞或器官的发育。」但另人振奋的是,研究人员在暴露于酒精的斑马鱼(zebrafish)胚胎中发现,给予胆固醇即能改善其因酒精导致的发育不良情况。
FAS会造成胎儿神经及心血管系统的发育缺陷,也会导致生长迟滞、颜面畸形以及智能不足等严重问题。根据统计,美国每天大约有100个出生婴儿患有FAS,每年花费在健保系统的费用大约有100亿美元。由于胆固醇很容易受到酒精的破坏,而胆固醇又是组成人体细胞膜的重要成份,因此,胆固醇含量不足对胎儿的发育是一大威胁。
Li博士说:「FAS的发生与酒精摄取量、持续的时间及怀孕的时期有很大的关联性,例如:在怀孕的第一个月会影响婴儿的脑部发育;第二个月则会影响胎儿脸部结构、心脏及视力的发育;第二至三个月时则会影响胎儿手指或足趾的生长。即使只是12盎司的啤酒都会影响胎儿的生长及发育,且母亲酒精的摄取量与胎儿发育不良的严重度成正比。」
Li博士指出:「补充适量的胆固醇除了可以改善FAS的问题,同样的也能预防酒精性肝病。」Li博士再次提醒怀孕妇女,在怀孕期间应确保摄取的胆固醇含量足够,以避免胎儿发育不良等严重问题的发生。
(资料来源 : Bio.com)
部分英文原文:
Laboratory Investigation 87, 231 - 240 (01 Mar 2007) Research Article
Fetal alcohol exposure impairs hedgehog cholesterol modification and signaling
Yin-Xiong Li1,2,3, Hai-Tao Yang1,5, Marzena Zdanowicz1,5, Jason K Sicklick1,4,5, Yi Qi1, Terese J Camp1 and Anna Mae Diehl1
1Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC, USA
2Department of Cell Biology, Duke University Medical Center, Durham, NC, USA
3Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
4Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Correspondence: Dr Y-X Li, MD, PhD, Department of Medicine, Duke University Medical Center, Snyderman-GSRB I, Suite 1073, 595 LaSalle Street, Box 3256, Durham, NC 27710, USA. E-mail: yinxiong.li@duke.edu
5These authors contributed equally to this work.
Abstract
Consumption of alcohol by pregnant women can cause fetal alcohol spectrum defects (FASD), a congenital disease, which is characterized by an array of developmental defects that include neurological, craniofacial, cardiac, and limb malformations, as well as generalized growth retardation. FASD remains a significant clinical challenge and an important social problem. Although there has been great progress in delineating the mechanisms contributing to alcohol-induced birth defects, gaps in our knowledge still remain; for instance, why does alcohol preferentially induce a spectrum of defects in specific organs and why is the spectrum of defects reproducible and predictable. In this study, we show that exposure of zebrafish embryos to low levels of alcohol during gastrulation blocks covalent modification of Sonic hedgehog by cholesterol. This leads to impaired Hh signal transduction and results in a dose-dependent spectrum of permanent developmental defects that closely resemble FASD. Furthermore, supplementing alcohol-exposed embryos with cholesterol rescues the loss of Shh signal transduction, and prevents embryos from developing FASD-like morphologic defects. Overall, we have shown that a simple post-translational modification defect in a key morphogen may contribute to an environmentally induced complex congenital syndrome. This insight into FASD pathogenesis may suggest novel strategies for preventing these common congenital defects.
Keywords:
fetal alcohol syndrome, fetal alcohol spectrum defects, hedgehog, cholesterol, post-translational modification, signal transduction
英文全文链接:http://www.nature.com/labinvest/journal/v87/n3/full/3700516a.html