维生素A缺乏对雌性大鼠生长发育及胚胎影响

目的建立维生素A（VA）完全及边缘缺乏的雌性大鼠模型,观察维生素A缺乏（VAD）对雌性大鼠及胚胎的影响。方法将初断乳SD雌性大鼠60只,随机分为VA缺乏组（AD）、VA边缘缺乏组（AM）、正常对照组（AN）,喂饲VA含量不同的饲料,耗竭性喂养后交配。将交配后的雌鼠在各组内随机分为VA缺乏组（A）、VA缺乏妊娠0d补充组（B）、VA边缘缺乏组（C）、VA边缘缺乏妊娠0d补充组（D）。B、D组于妊娠第0d喂饲补充饲料。于妊娠第19.5d将所有孕鼠处死并观察胚胎发育情况。结果发生AD组雌鼠出现明显的生长发育抑制。A组胚胎全为吸收胎,C组胚胎生长发育明显低于AN及B、C组,而畸胎死胎出现率明显高于AN及B、C组。结论VAD可明显影响雌性大鼠及其胚胎的生长发育,孕期补充VA可有效降低VAD对胚胎的发育毒性。     

维生素A、锌、铜、钙对眼组织及视力的影响

本实验分别对动物和人群进行了维生素Ａ、锌、铜、钙与眼组织及视力关系的研究。动物实验主要观察维生素Ａ和锌对眼组织的影响。动物为封闭群Ｗｉｓｔａｒ健康大鼠，平均体重７４±１７ｇ，随机分为四组，实验期２５天，主要观察的指标为血清、肝脏和眼球中的维生素Ａ含量、血清锌含量以及眼球组织变化。结果表明，在维生素Ａ缺乏的情况下，摄入低锌时血清、肝脏和眼球的维生素Ａ含量明显低于摄入高锌者；当维生素Ａ供给充足时，低锌组与高锌组血清及各组织中的维生素Ａ含量无明显差别。提示，锌对眼球维生素Ａ含量的影响与维生素Ａ的水平及摄入量有关。人群实验主要观察了血清维生素Ａ、锌、铜、钙对视力的影响。筛选７２名一眼或双眼裸眼视力小于１．２的学生作为实验组，２３名双眼裸视力均在１．５以上者作为对照组。经检测，实验组血清锌、钙明显低于对照组，而铜、维生素Ａ含量在两组间无明显差别，说明体内锌、钙降低与近视有一定关系，而铜、维生素Ａ在本实验中未发现与近视有明显相关。     

孕妇的微量营养素状况亟待关注

新中国成立以来 ,特别是改革开放 2 0多年来 ,我国居民的营养状况得到了明显改善 ,过去的经典营养缺乏病 ,例如严重蛋白质和能量营养不良、维生素Ａ或硫胺素缺乏病的发生率显著下降。然而 ,育龄期妇女的微量营养素缺乏或边缘性缺乏的发生率还较高 ,并且还没有引起充分的重视 ,例如缺铁和缺铁性贫血 ,维生素Ａ、碘、钙、锌以及Ｂ族维生素的边缘性缺乏。贫血、佝偻病、维生素Ａ和锌缺乏等营养缺乏病仍然是影响孕妇健康和出生婴儿质量的重要营养问题 ,孕期甚至孕前缺乏微量营养素不仅影响孕妇的健康状况 ,也可能对胎儿以及婴儿的生长发育产生长…     

补充维生素A对儿童生长发育的影响

４６９名６～４８月儿童随机分为实验组和对照组，以探讨在维生素Ａ缺乏地区儿童中一年２次补充大剂量维生素Ａ（每次２０×１０￣４ＩＵＶ＿Ａ和４０ＩＵＶ＿Ｅ）对其生长发育的作用。１２个月的观察表明，实验组儿童体重增长速度明显高于对照组（Ｐ＜０．０１），从６～３６月龄儿童实验和对照组相差３００±６９ｇ至５０±６ｇ。３６月龄儿童实验组身高增长高于对照组（Ｐ＜０．０１），其余各年龄组间无明显差异（Ｐ＞０．０５），但实验组儿童有高于对照组的趋势。本实验结果提示，在维生素Ａ缺乏地区补充维生素Ａ可以改善儿童的生长发育水平，尤其是体重的增长。     

双酚A致体外培养大鼠胚胎发育毒性的时间-效应关系研究

目的探讨双酚A（BisphenolA）对大鼠胚胎毒性的时间-效应关系。方法采用全胚胎培养模型,对9.5d龄大鼠胚胎分别染毒BisphenolA（100mg/L）6、16、26、48h,观察体外培养胚胎生长发育的影响。结果早期暴露6h对体外培养的大鼠胚胎的生长发育无不良影响,染毒16h即可影响大鼠胚胎的生长发育,染毒26h和48h对胚胎生长发育和形态分化均有明显的抑制作用。光镜下发现只有染毒26h以上才出现卵黄囊及大鼠胚胎脑组织结构的改变。结论体外实验条件下,BPA对器官形成期的早期大鼠胚胎的毒性作用具有明显的时间-效应关系,其毒性表现为慢性毒性作用。     

钙、维生素D缺乏对幼鼠骨生长和成骨细胞功能的影响

目的：探讨钙与维生素D营养缺乏对幼鼠骨骼生长和矿化的影响及机制。方法：建立单纯钙缺乏、维生素D缺乏和钙与维生素D同时缺乏的幼鼠动物模型，追踪其长骨的生长发育，并监测血清Ca,P,25-ODH3,骨碱性磷酸酶（B－ALP）水平及骨矿含量的构成的改变；观察反映骨形成和成骨细胞功能的生化标志－血清骨钙素水平。结果：钙缺乏、维生素D缺乏和两者同时缺乏大鼠的长骨生长发育明显落后于正常大鼠；其胫骨重、骨灰重均显著降低；对骨矿成分的分析显示，除K以外Ca,P,Mg,Na均有不同程度减少；实验组大鼠的血清骨钙素水平随实验期延长呈进行性下降。结论：钙和维生素D缺乏影响成骨细胞的功能，使骨形成和矿化过程受阻，从而导致骨骼生长发育质和量的异常。     

维生素A缺乏对大鼠铁调节蛋白2影响

目的 探讨维生素A缺乏对大鼠铁调节蛋白2(IRP2)mRNA及铁蛋白(Fn) nRNA和转铁蛋白受体(TfR)mRNA表达影响.方法48只雄性SD大鼠按体重随机分为4组,每组12只,对照组、维生素A完全缺乏组;维生素A边缘缺乏组;铁及维生素A边缘缺乏组;喂养8周后,麻醉处死大鼠,取组织和血清,进行相关指标和基因表达检测.结果与对照组( 1.50 +0.41) μmol/L比较,维生素A完全缺乏大鼠血清维生素A(0.22±0.26) μmol/L水平明显降低(P＜0.05);与对照组比较,维生素A完全缺乏组大鼠血清铁(2.26 +0.72)lμg/mL明显降低;维生素A完全缺乏组大鼠肝脏IRP2、TfR表达水平分别为(1.53±0.18)、(0.62±0.06)与对照组相比明显升高,FnmRNA (0.52±0.08),明显低于对照组(P＜0.05).结论维生素A缺乏通过改变IRP2表达、IRP-RNA结合活性,在转录后水平改变TfR和Fn mRNA表达,影响铁稳态.     

VitA对小鼠胚胎组织Hox gene蛋白表达的影响

目的：从发育基因角度探讨维生素A（VA）缺乏导致先天性畸形的机理,方法。通过建立小鼠VA缺乏模型,用免疫组织化学等方法研究VA缺乏对小鼠胚胎组织Hox gene蛋白表达水平的影响。结果：维生素A缺乏使胎鼠的Hox gene蛋白表达明显低于正常对照组（P＜0．05）。VA补充组明显高于VA缺乏组,但仍比正常对照组低,结论：VA缺乏可能在翻译水平影响小鼠胚胎组织Hox gene蛋白表达。     

营养干预对学龄前儿童血清锌及维生素A营养状况的影响

锌和维生素Ａ（ＶＡ）都是促进人体生长发育的重要微量营养素,两者在体内的营养水平可影响儿童的生长发育。Ｓｔｅｖｅｎ－ｓｏｎ等人曾报道〔１〕,锌可以帮助治疗家畜猪ＶＡ缺乏病。Ｃａｒｎｅｙ等人采用放谢性标记的方法〔２〕,观察大鼠肝脏在１周内释放ＶＡ的情况,...     

应用全胚胎培养方法研究CrCl_3对大、小鼠胚胎的发育毒性研究

目的　研究三价铬化合物的发育毒性及其种属差异。方法　采用植入后大、小鼠全胚胎培养技术 ,观察胚胎生长发育及组织分化的改变。结果　三氯化铬 (CrCl3 )影响大、小鼠胚胎的生长发育 ,CrCl3 对大鼠或小鼠胚胎作用浓度在 112 5 μmol/L或 15 0 0 μmol/L以上时可导致大、小鼠胚胎体长、头长、卵黄囊直径及胚胎干重等指标明显低于对照组 ,形态学评分结果可见 ,CrCl3 主要影响大、小鼠胚胎神经管、体屈、前肢芽及鳃弓等形态分化 ,高浓度组还可导致胚胎畸形发生率的明显升高。结论　表明CrCl3 对体外培养的大、小鼠胚胎具有明显的发育毒性 ,且大鼠较小鼠敏感     

Vitam A deficiency and fetal growth and development in the rat.

Studies were conducted to examine in detail the effects of vitamin A deficiency on fetal growth and development in the rat. The gradations of deficiency were examined in two studies. The first included total vitamin A depletion followed by retinoic acid supplements, and the second included three different levels of restricted intake of retinyl acetate (42, 16, or 8 mug of retinol equivalents/day/kg of body weight) in vitamin A-depleted rats. In the first study, extensive fetal resorption and death were observed in retinoic acid-fed females after day 14 of gestation. These findings confirmed the morphological studies of Thompson and associates (Proc. Roy. Soc. London, Ser. B 159, 510-535, 1964) who found the earliest Detectable histological lesions to be in the placentas at days 15-16 of pregnancy. Analyses were carried out of the total weight, the DNA, RNA, and protein contents of fetuses and placentas of different gestational ages in retinyl ester-fed and retinoic acid-fed females. Biochemical changes indicative of a reduced rate of cell division were observed in both fetus and placenta by day 14 in the retinoic acid-fed rats. The few live fetuses in this group maintained a growth rate of only 60-70% of that of the fetuses of retinyl ester-fed dams after day 14. By contrast, the growth rate of the placentas (of live fetuses) after day 14 of gestation was not as consistently affected by retinol deficiency. Restriction of retinyl acetate intake (in the second study) significantly reduced both the total litter size and the number of live pups per litter. Most of the females in the retinyl acetate-restricted groups delivered pups that had normal body weight and appeared normal on visual inspection. Significant differences from normal controls were seen only in the neonates from dams given 8 mug of retinol equivalents (per kg of body weight per day), which had smaller livers and kidneys than the control neonates. In contrast, the weights of the brains of the neonates in all three retinyl acetate-restricted groups showed no differences from control values. Vitamin A assays on maternal and neonatal sera and livers indicated that the transport of vitamin A across the placenta was well regulated, and suggested that this transport is maintained with high priority in the presence of maternal deficiency. The effects of vitamin A deficiency on fetal growth and development might reflect primary effects on the placenta, with secondary effects on the fetus, or primary direct effects on the fetus itself. The mechanisms of the observed effects remain to be explained.     

Moderate maternal vitamin A deficiency affects perinatal organ growth and development in rats

Vitamin A deficiency during pregnancy is associated with detrimental effects in the offspring. We have developed a rat model to examine specific effects of maternal vitamin A status on perinatal growth and development. A total of 54 female rats were fed a vitamin A-free (VAF), -marginal (VAM) or -sufficient (VAS) diet from weaning until mating (at 7 weeks) and throughout pregnancy. Half of the rats in each group were injected with a single large dose of vitamin A on day 10 of pregnancy. Fetal and neonatal samples were taken on day 20 of pregnancy and the day of birth respectively. Maternal plasma retinol concentrations on day 20 and at birth were 50% and 30% lower in the VAF and VAM when compared to the VAS group. Fetal weight and survival did not differ between groups although placental:fetal ratio was higher in the VAF group than in the VAS group (0.195 (SE 0.005) v. 0.175 (SE 0.004), P < 0.05). Rats fed the VAF diet gave birth at 23.5 d, an average of 1 d later than the other groups, and had lower number of live neonates at birth. Fetal liver, heart and lung weights relative to total body weight were lower in the VAF group and had altered growth trajectories. In neonates, only the relative lung weight was reduced. In addition, an increased protein:DNA ratio indicated hypertrophy in fetal kidneys. Vitamin A injection had no additional effect on length of gestation and fetal or neonatal number. However, injection increased relative fetal organ weights in the VAF group but did not alter the effects of vitamin A deficiency in the neonate. These data suggest that chronic vitamin A deficiency during pregnancy compromises liver, heart and kidney and impairs lung growth and development during the last few days of gestation and reduces number of live neonates at birth.     

苯对大鼠的生殖毒性和胚胎发育毒性研究

目的探讨苯对大鼠的生殖毒性和胚胎的体内发育毒性。方法以浓度分别为0、5、10、15mg/m3的苯给雌雄性大鼠静式吸入染毒,观察雄性大鼠精子畸形和雌雄交配受孕情况、受精卵着床数、活胎数、死胎数、吸收胎数及胚胎的生长发育情况。结果苯染毒组大鼠精子畸形率高于空白对照组,随着苯染毒浓度的增加,畸形率有增加(P0.05);与空白对照组比较,中、高剂量苯染毒可抑制胎盘和胎仔生长发育,吸收、死胎发生率增加(P0.05)。结论苯具有雄性生殖毒性,并对胚胎有一定的致畸性作用和发育毒性。     

维生素A缺乏对小鼠胚胎Hox基因表达的影响

目的：观察维生素Ａ（ＶＡ）缺乏对小鼠胚胎ＨｏｘＣ４（３．５）和ＨｏｘＤ１０（４．５）基因表达量的影响。方法：初断乳的昆明小鼠,雌鼠４０ 只均分为正常对照组（Ａ）和维生素Ａ缺乏组（Ｂ）,分别饲含ＶＡ４０００ ＩＵ／ｋｇ 饲料和ＶＡ ０ ＩＵ／ｋｇ 饲料。雄鼠饲以普通饲料。在饲养的第１７ 周按雌∶雄＝ ２∶１ 合笼交配。在怀孕的第１２ 天和第１４ 天,分别对孕鼠颈椎脱臼处死,立刻剖腹取出胎鼠,迅速置于液氮中速冻后置于－ ７０℃冰箱保存。用地高辛标记的探针,采用原位杂交方法探测小鼠胎儿ＨｏｘＣ４（３．５）和ＨｏｘＤ１０（４．５）基因ｍ ＲＮＡ含量。结果：ＶＡ缺乏时,ｍ ＲＮＡ的含量明显减少。结论：ＶＡ缺乏导致Ｈｏｘ 基因表达量下降,从而影响小鼠胚胎的正常发育。     

Vitamin A in reproduction and development

The requirement for vitamin A in reproduction was first recognized in the early 1900's, and its importance in the eyes of developing embryos was realized shortly after. A greater understanding of the large number of developmental processes that require vitamin A emerged first from nutritional deficiency studies in rat embryos, and later from genetic studies in mice. It is now generally believed that all-trans retinoic acid (RA) is the form of vitamin A that supports both male and female reproduction as well as embryonic development. This conclusion is based on the ability to reverse most reproductive and developmental blocks found in vitamin A deficiency induced either by nutritional or genetic means with RA, and the ability to recapitulate the majority of embryonic defects in retinoic acid receptor compound null mutants. The activity of the catabolic CYP26 enzymes in determining what tissues have access to RA has emerged as a key regulatory mechanism, and helps to explain why exogenous RA can rescue many vitamin A deficiency defects. In severely vitamin A-deficient (VAD) female rats, reproduction fails prior to implantation, whereas in VAD pregnant rats given small amounts of carotene or supported on limiting quantities of RA early in organogenesis, embryos form but show a collection of defects called the vitamin A deficiency syndrome or late vitamin A deficiency. Vitamin A is also essential for the maintenance of the male genital tract and spermatogenesis. Recent studies show that vitamin A participates in a signaling mechanism to initiate meiosis in the female gonad during embryogenesis, and in the male gonad postnatally. Both nutritional and genetic approaches are being used to elucidate the vitamin A-dependent pathways upon which these processes depend.     

Nutritional Control of Fetal Growth

Maternal micronutrient nutrition is an important determinant of size and body composition of the fetus. Maternal iron, iodine, calcium, folate, vitamin A, and vitamin C nutrition all influence offspring size. The Pune Maternal Nutrition Study was designed to study the relationship between maternal nutrition and fetal growth, size at birth, and postnatal growth. Maternal circulating folate and vitamin C concentrations predicted larger offspring size, while higher ferritin levels predicted smaller-sized babies. Subclinical vitamin B₁₂ deficiency is common in India, especially in vegetarians, and children born to mothers with the lowest vitamin B₁₂ but the highest folate status were the most adipose and the most insulin resistant. Furthermore, the relationship between maternal nutrition, fetal growth, and risk of type 2 diabetes and coronary heart disease appears to be much more complex than the simplistic postulates of the "fetal origins" hypothesis.     

新生儿维生素A缺乏的研究进展

维生素A是机体重要的脂溶性维生素,参与机体多种功能,在小儿生长发育方面发挥重要作用。新生儿期维生素A 缺乏与其生后疾病的发生密切相关。在具有维生素A缺乏风险的国家,新生儿补充维生素A已经成为国家政策。但是目前很多研究对这一政策提出质疑。该文对新生儿维生素A缺乏研究进展作一综述,以便更好地指导临床诊疗。     

Lipid composition and metabolism in liver and brain of vitamin B12-deficient rat sucklings.

1. Rat sucklings (18-d-old) bred from vitamin B12-deprived dams were compared with vitamin B12-supplemented dams' offspring, which were considered normal rat sucklings. 2. The vitamin B12-deficient rat sucklings had lower body-weight, liver weight and brain weight. 3. Vitamin B12 deficiency was also evident from the tenfold lower concentrations of vitamin B12 in liver and cerebellum. 4. The concentration of liver lipid was markedly increased in vitamin B12-deficient rats; triacylglycerol accounted for most of the increase. In brain the lipid concentration was slightly decreased (less than 0.05). 5. The methylation of ethanolamine phosphoglyceride to choline phosphoglyceride was reduced in both liver and brain in vitamin B12-deficient rats, as measured after the administration of [14C]ethanolamine. A slight decrease in choline phosphoglyceride concentration could be a consequence of this finding. The composition of phospholipids was otherwise normal. 6. Odd-chain fatty acids (pentadecanoate and heptadecanoate) accumulated in both liver and brain of the vitamin B12-deficient rat sucklings and constituted approximately 1% of total fatty acid. 7. The biosynthesis of fatty acid and cholesterol from intraperitoneally-injected 3H2O and [14C]propionate was unchanged in vitamin B12 deficiency.     

DNA microarray technology reveals similar gene expression patterns in rats with vitamin a deficiency and chemically induced colitis

Previous studies suggest that vitamin A deficiency may induce or intensify inflammatory changes in the rat gastrointestinal system. The present study was designed to compare the expression profiles of rat models of vitamin A deficiency and induced colitis. cDNA-microarray technology was used to determine the genes involved in the inflammatory processes in the two models. mRNA was extracted from colons of rats that were vitamin A deficient, vitamin A supplemented (control), or had 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis, reverse-transcribed into fluorescence-labeled cDNA and hybridized onto microarrays containing a duplicate set of 1152 cDNAs, derived mainly from the colon carcinoma cell line Caco-2. Differential gene expression was detected in vitamin A deficiency and in TNBS-induced colitis vs. control. beta-Actin, translation initiation factor A4 and translation elongation factor 1, ornithine decarboxylase (ODC) and keratin 19 were markedly down-regulated, whereas spermidine/spermine N1-acetyltransferase (SSAT) and polyubiquitin (UbC) were up-regulated in both vitamin A-deficient rats and those with TNBS-induced colitis. The strong association between the differential gene expression in the two animal models, compared with the control, suggests that deficiency of vitamin A causes inflammatory changes in the rat colon that are similar to processes occurring in colitis. Further investigation is required to elucidate the importance of each of the regulated genes to the pathology of colitis and vitamin A inadequacy.     

Effect of pyridoxine deficiency and prednisolone on beta-alanine-oxoglutarate aminotransferase and D-3-aminoisobutyrate aminotransferase in rat liver and kidney

beta-Alanine-oxoglutarate aminotransferase (beta-Ala-TI) was found to be distributed mainly in liver, brain, kidney, and testis (decreasing order of enzyme activity in the rat). D-3-Aminoisobutyrate aminotransferase (beta-Ala-T II) was distributed in kidney and liver. Both beta-Ala-T I and beta-Ala-T II were localized in the mitochondrial fraction in rat kidney. beta-Ala-T I in the liver of rats fed on pyridoxine-deficient or control diets was induced by injecting with prednisolone, while beta-Ala-T II in the liver of these rats was unaffected by prednisolone injection. The activities of beta-Ala-T I and beta-Ala-T II in the liver of rats fed on pyridoxine deficient diet did not change. However, in kidney, pyridoxine deficiency suppressed both enzyme activities, while treatment with prednisolone did not induce either enzyme. The ratios of the apo- to holo-enzyme for beta-Ala-T I and beta-Ala-T II in control rat kidney were 1.04 and 0.11, respectively. The values increased to 2.69 and 1.53, respectively, in pyridoxine-deficient rat kidney. These experiments indicate that pyridoxine deficiency and prednisolone affect the activities of beta-alanine degrading enzymes, but that the degree is different between liver and kidney.