中文摘要：

目的：探讨维生素 A 缺乏导致新生大鼠枕颈部畸形的作用机制。方法：将40只5周龄雌性健康 SPF 级 SD 大鼠随机分为2组，正常对照组20只，维生素 A 缺乏组20只；20只适龄雄性健康 SPF 级 SD 大鼠分笼饲养。正常对照组饲以 AIN －93M饲料，维生素 A 缺乏组饲以缺乏维生素 A 的 AIN －93M饲料，雄性大鼠饲以 AIN －93M饲料。饲养至第10周从雌性大鼠的目外眦取血，采用酶联免疫吸附法检测2组雌鼠血清维生素 A 含量，鉴定大鼠模型。造模成功后，将大鼠按雌2雄1的比例合笼交配，第2天清晨检查阴栓，有阴栓者记为 E0 d。于妊娠 E11．5 d 取2组半数的孕鼠，麻醉处死后剖腹，每只孕鼠取出2只胚胎，剥离被膜，置于液氮中，然后转移至－80℃的冰箱里保存待测。于妊娠 E21 d 取新生鼠，麻醉处死后剥离皮肤筋膜以及内脏，置于95％的酒精中固定待测。采用 RT －qPCR 方法检测胚胎 Hoxd3基因 mRNA 表达情况；采用双色染色法制作大鼠骨骼标本，观察新生鼠枕颈部骨骼发育情况。结果：①雌鼠血清维生素 A 含量。维生素 A 缺乏组大鼠血清维生素 A 含量明显低于正常对照组[（214±39）ng·mL －1，（432±54）ng·mL －1，t ＝14．636，P ＝0．000]。②胚胎 Hoxd3基因 mRNA 的表达量。维生素 A 缺乏组胚胎 Hoxd3基因表达量低于正常对照组（0．58±0．11，1．03±0．14，t ＝10．407，P ＝0．000）。③新生鼠枕颈部骨骼形态。正常对照组可见枕骨与寰枢椎发育正常，对位关系良好；维生素 A 缺乏组可见寰椎后弓与枕骨大孔后缘角度增大，寰枢椎对位关系异常，寰枢椎后弓角度增大，C2～C7椎弓及棘突高度降低、宽度变窄，且相邻椎体间隙增大。结论：维生素 A 缺乏可以导致新生大鼠枕颈部结构发育异常，这可能与其胚胎发育期 Hoxd3基因 mRNA 表达水平下降有关，但其具体的分子生物学机制?

英文摘要：

Objective：To explore the mechanism of occipito -cervical deformity induced by vitamin A deficiency in neonatal rats. Methods：Forty healthy 5 -week -old female SPF -grade SD rats were randomly divided into 2 groups,20 rats in each group.The female rats were respectively fed with normal AIN -93Mstoyer（normal control group）and AIN -93Mstoyer lacking in vitamin A（vitamin A defi-ciency group,VAD group）.Meanwhile,20 healthy male SPF -grade SD rats were recruited and fed with AIN -93Mstoyer in separate ca-ges.Ten weeks later,serum content of vitamin A were detected in female rats by enzyme -linked immunosorbent assay to identify the rat models.After successful modeling,the rats were mated according to the female -male ratio of 2：1 .In the next morning,the female rats were examined in vaginal plug and rats which had vaginal plug were recorded as E0 d.At 1 1 .5 days after gestation,half of the pregnant rats were anesthetized and sacrificed.The belly of each pregnant rat were cut open and two embryos were fetched out and their capsules were stripped.The embryos were placed in liquid nitrogen and then were transferred to refrigerator and reserved at -80 ℃.On 21 st gestational day,neonatal rats were anesthetized and sacrificed.Their skins and fascias were stripped and their internal organs were removed.Then the neonatal rats were reserved in 95% alcohol.The qRT -PCR assays was used for detecting the Hoxd3 mRNA expression in embryos and the bicolor staining method was used for observing the development of occipito -cervical bone of neonatal rats.Results：The serum contents of vitamin A were obviously lower in the VAD group compared to the control group（21 4 ＋/-39 vs 432 ＋/-54 ng/mL,t =1 4.636,P =0.000）.The Hoxd3 mRNA expression in embryos was obviously lower in the VAD group compared to the control group（0.58 ＋/-0.1 1 vs 1 .03 ＋/-0.1 4,t =1 0.407,P =0.000）.Normally developed occipital bone,atlas and axis and right contraposition of atlanto -axial joint were found in the control group.However,i