杜克大學(xué)醫(yī)學(xué)中心(Duke University Medical Center)的研究人員發(fā)現(xiàn),，膽固醇也許可以預(yù)防胎兒酒精癥候群(Fetal Alcohol Syndrome,，以下簡(jiǎn)稱FAS)。此研究發(fā)表于3月份的Laboratory Investigation期刊。研究經(jīng)費(fèi)由NIH(National Institutes of Health)及AHA(American Heart Association)資助。
膽固醇對(duì)胎兒的發(fā)育扮演相當(dāng)重要的角色,，懷孕婦女即使滴酒不沾，若其膽固醇量不足也會(huì)造成胎兒發(fā)育上的許多問題,。Yin-Xiong Li博士說：「即使很少量的酒精,，都會(huì)阻擾胚胎中細(xì)胞或器官的發(fā)育?！沟砣苏駣^的是,，研究人員在暴露于酒精的斑馬魚(zebrafish)胚胎中發(fā)現(xiàn)，給予膽固醇即能改善其因酒精導(dǎo)致的發(fā)育不良情況,。
FAS會(huì)造成胎兒神經(jīng)及心血管系統(tǒng)的發(fā)育缺陷,，也會(huì)導(dǎo)致生長遲滯、顏面畸形以及智能不足等嚴(yán)重問題,。根據(jù)統(tǒng)計(jì)，美國每天大約有100個(gè)出生嬰兒患有FAS,，每年花費(fèi)在健保系統(tǒng)的費(fèi)用大約有100億美元,。由于膽固醇很容易受到酒精的破壞，而膽固醇又是組成人體細(xì)胞膜的重要成份,，因此,，膽固醇含量不足對(duì)胎兒的發(fā)育是一大威脅。
Li博士說：「FAS的發(fā)生與酒精攝取量,、持續(xù)的時(shí)間及懷孕的時(shí)期有很大的關(guān)聯(lián)性,，例如：在懷孕的第一個(gè)月會(huì)影響嬰兒的腦部發(fā)育；第二個(gè)月則會(huì)影響胎兒臉部結(jié)構(gòu),、心臟及視力的發(fā)育,；第二至三個(gè)月時(shí)則會(huì)影響胎兒手指或足趾的生長。即使只是12盎司的啤酒都會(huì)影響胎兒的生長及發(fā)育,，且母親酒精的攝取量與胎兒發(fā)育不良的嚴(yán)重度成正比,?！?/p>
Li博士指出：「補(bǔ)充適量的膽固醇除了可以改善FAS的問題，同樣的也能預(yù)防酒精性肝病,?！筁i博士再次提醒懷孕婦女，在懷孕期間應(yīng)確保攝取的膽固醇含量足夠,，以避免胎兒發(fā)育不良等嚴(yán)重問題的發(fā)生,。
(資料來源 : 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: [email protected]
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
英文全文鏈接：http://www.nature.com/labinvest/journal/v87/n3/full/3700516a.html
