边缘VA缺乏对大鼠胚胎骨骼发育及视黄酸受体表达的影响

目的研究边缘性维生素A(VA)缺乏及补充对大鼠胚胎骨骼发育的影响,及其与视黄酸受体(RARs)基因表达的关联性。方法初断乳SD雌性大鼠30只,按体重随机分为边缘性VA缺乏组(AM),边缘性VA缺乏妊娠0d(E0d)补充组(AS)和正常对照组(AN)。AM和AS组喂饲边缘性VA缺乏饲料(含VA0.4IU/gdiet),AN组喂饲VA充足饲料(含VA4IU/gdiet)。60d后与正常雄鼠交配。AS组自E0起改喂VA补充饲料(含VA10IU/gdiet)。于E12.5d和E19.5d将孕鼠处死,取胚胎。观测E19.5d胚胎骨骼发育指标;用荧光定量PCR及Westernblot检测E12.5d胚胎组织视黄酸受体的表达。结果AM组97.2%的E19.5d胚胎骨骼发育明显迟缓并出现多种骨骼畸形;E12.5d胚胎RARβ、RARγ表达水平明显下降。AS组胚胎各指标较AN组无异。结论视黄酸受体参与介导边缘性VA缺乏导致的大鼠胚胎骨骼发育异常,孕早期补充VA可有效预防骨骼畸形的发生。

EFFECTS OF MARGINAL VITAMIN A DEFICIENCY ON SKELETON DEVELOPMENT AND EXPRESSION OF RETINOIC ACID RECEPTORS OF RAT EMBRYOS

Objective To investigate the association between the effects of marginal vitamin A deficiency and supplement on skeleton development and the expression of retinoic acid receptors of rat embryos. Methods The weaning female SD rats were randomly divided into 3 groups, marginal VA deficiency group (AM), VA-supplement group (AS), VA normal group (AN). The VA contents in diet were: 0.4 IU/g diet (AM, AS), 4 IU/g diet (AN). After 60 d, the female rats were mated with male rats. The AS group shift to AS diet (10 IU/g diet) on E0 d. All rats were sacrificed on E12.5 or E19.5. The skeleton development was surveyed on E19.5 embryos. The retinoic acid receptors (RARs) expression was detected with SYBR Green RT-PCR and Western blot on El2.5 embryos. Results The expression of RARp and RARγ and the skeleton development of embryos of AM group were reduced significantly than those of control group, whereas there was no difference of these indices in AS group relative to control group. Conclusion The RARs paly an essential role in mediating the skeleton malformation resulting from marginal VA-deficiency, and VA-supplement in early pregnancy is effective to prevent this abnormality.