不同剂量锌缺乏对小鼠及其胚胎发育的影响

目的 :　用昆明种雌性小鼠建立成不同程度缺锌动物模型 ,研究不同程度锌缺乏和孕早期补锌对小鼠及其胚胎发育的影响 ,并探求其发育毒性作用的阈剂量。方法 :　实验分两阶段进行。实验一用 36只初断乳 1 4～ 1 8g小鼠 ,分为低锌 (ZD)、中锌 (ZM)、常锌 (ZN)三组 ,喂饲含锌分别为 3.0± 0 .5、1 5、30 mg/kg的饲料 ,经 50 d喂养平均体重达 30 g后交配。实验二选用 80只 ,2 5～ 30 g成熟小鼠 ,随机分为低锌组 [ZD,饲料含锌 (3.0± 0 .5) mg/kg];低锌补锌组 (ZS,于孕第 7d将低锌饲料换为含锌 30 mg/kg的常锌饲料 ) ;边缘缺锌组 (MD,饲料含锌 9mg/kg) ;常锌组(ZN,饲料含锌 30 mg/kg)。 2 5d锌耗竭性喂养后交配。所有孕鼠于妊第 1 8d活杀。结果 :　实验一 :低锌组小鼠锌水平显著低于常锌组 (P<0 .0 5) ,有典型缺锌症状 ,几乎全部出现生长抑制 ,58.33%的小鼠衰竭死亡 ,存活小鼠亦不能正常交配妊娠。 1 5mg/kg剂量组小鼠则生长发育良好 ,各项指标与常锌组间无异 (P>0 .0 5)。实验二 :ZD组小鼠血清碱性磷酸酶 (AKP)活性 ,股骨锌含量显著低于 ZN组 (P<0 .0 1 ) ;该组小鼠胚胎有明显发育不良 ,畸胎及死胎出现率显著高于 ZN组 (P<0 .0 1 )。ZS组小鼠在孕第 7d补锌后活胎仔大小已趋正常 (P>0 .0 5) ,畸胎出现率与 ZD?     

锌缺乏对孕鼠发育及体内促生长有关激素水平的影响

目的　探讨锌缺乏对妊娠大鼠发育及体内促生长有关激素含量的影响。方法　将Wistar妊娠大鼠随机分为缺锌组 (ZD)、对喂组 (PF)、补锌组 (ZS)及正常对照组 (Cont) ,分别给予缺锌 (0 .7mg/ kg)和正常锌 (1 0 0 mg/ kg)饲料喂养 ,观察孕鼠及胎鼠发育情况 ,并采用放射免疫法检测血清中甲状腺素 (T3 、T4 )、促甲状腺素 (TSH)和生长激素 (GH)含量。结果　缺锌组孕鼠在妊娠期间体重没有增加 ;胎鼠出生体重显著低于其他三组 ;血清中激素含量显著低于补锌组和正常对照组。结论　锌缺乏可降低孕鼠血液中促生长有关激素含量 ,导致孕鼠及胎儿生长发育迟缓。     

缺锌对0～2月龄大鼠免疫功能影响的研究

目的 观察缺锌对0～2月龄大鼠免疫器官及细胞因子分泌的影响,为进一步阐明缺锌影响免疫系统的机制及对婴幼儿期、青少年期合理补锌提供参考依据.方法 将9只Wistar孕鼠产仔后随机分为足锌(ZA)、对喂(PF)和缺锌(ZD)3组,每组3只母鼠.ZA组和PF组喂饲足锌饲料(30mg/kg),ZD组喂饲缺锌饲料(1.Omg/k...     

缺锌并补锌对大鼠睾丸及血清睾酮的影响

目的　为了解锌缺乏及补锌对大鼠睾丸的重量及血清睾酮的影响。　方法　将出生后断乳一周的SD大鼠随机分为缺锌组、配喂组、对照组、补锌组和高锌组五组 ,缺锌组、对照组和高锌组分别用缺锌饲料 (锌含量 <1mg/kg)、常锌饲料 (锌含量为 5 0mg/kg)和高锌饲料 (锌含量为 15 0mg/kg)喂养 8周 ,补锌组用缺锌饲料喂养三周后改用高锌饲料喂养五周 ,配喂组用常锌饲料喂养 ,给料量按缺锌组前一天实际进食量添加。 8周后处死 ,用极谱法测定血清中锌含量 ,用原子吸收分光光度法测定睾丸中锌含量 ,采用双抗体放射免疫分析法测定血清中睾酮的含量。　结果　缺锌组大鼠睾丸及血清中锌含量降低 ,睾丸重量减轻。血清中睾酮含量下降 ,缺锌大鼠补锌后可恢复正常。　结论　说明锌缺乏直接影响睾丸及血清中锌的水平 ,从而影响大鼠睾丸的发育及睾酮的分泌与合成。     

维生素A和锌营养水平与小鼠胚胎HOX基因表达的相关性

目的 研究不同维生素A、锌营养水平与小鼠胚胎HOX C4（3.5）基因表达的相关关系。方法 昆明种雌鼠随机均分为3组;缺乏组喂饲无维生素A和低锌饲料;补充组：开始时饲料同缺乏组,母鼠受孕第7天改为富含维生素A和锌的饲料;正常组自始至终喂饲正常饲料。动物喂养至出现明显维生素A、锌缺乏症状后进行交配。受孕第12天取出相应数量孕鼠处死,取样测生化指标;取胚胎测定HOX C4(3.5）基因mRNA表达量。结果 缺乏组、补充组和正常组母鼠血清维生素A水平均值分别为0.44umol/L、1.03umol/L和1.40umol/L,股骨锌含量均值分别为124.3mg/kg、152.1mg/kg和193.8mg/kg,差异有显性。胚胎HOX C4（3.5)基因表达也显升高。结论 小鼠机体维生素A和锌营养水平与胎鼠HOX C4(3.5）基因表达呈高度正相关,各项指标相关系数为0.78～0.99。     

缺锌及补锌对大鼠甲状腺激素的影响

目的了解锌缺乏及补锌对大鼠甲状腺激素的影响。方法将出生后断乳1周的SD大鼠随机分为缺锌组、配喂组、对照组、补锌组和高锌组,缺锌组、对照组、高锌组分别用缺锌饲料(Zn含量<1mg/kg),常锌饲料(Zn含量为50mg/kg)和高锌饲料(Zn含量为150mg/kg)喂养8周,补锌组用缺锌饲料喂养3周后改用高锌饲料喂养5周,配喂组用常锌饲料喂养,给料量按缺锌组前一天实际进食量添加。8周后处死,用极谱法测定血清中锌的含量,用放射免疫法测定血清中FT3、FT4的含量。结果缺锌使大鼠血清中锌含量显著降低,血清中FT3含量下降,补锌后恢复正常,缺锌对FT4无影响。结论缺锌引起甲状腺激素FT3下降,而FT4不受影响。     

锌缺乏对孕鼠及其胎鼠体内元素分布的影响

为了解锌缺乏对妊娠大鼠及胎鼠体内元素分布的影响 ,将Wistar妊娠大鼠分为缺锌组、对喂组、补锌组和对照组 ,分别喂饲缺锌 (0 7mg kg)和正常锌 (10 0mg kg)饲料 ,在妊娠第 2 1天时处死孕鼠 ,取其血液、肝、脾、肾、胎盘和胎鼠 ,用原子吸收分光光度法测定锌、铜、铁、锰、钙含量。结果表明 ,缺锌组孕鼠各组织中锌和其他元素含量均显著低于补锌组和对照组 ;而且其血液、肝、脾、肾脏中铜、铁、锰含量显著低于对喂组 ,说明锌和其他元素在肠道吸收和组织分布方面存在协同关系 ,锌缺乏所致的动物摄食量减少不是引起组织中元素含量降低的主要原因。缺锌组胎盘中铁和胎鼠中铁、钙含量则显著高于其他三组 ,反映了锌与铁元素在胎盘可能存在竞争性转运。提示锌缺乏的母体和胎儿各元素在组织中分布不一致。     

营养

01.1760锌缺乏对培养小鼠胚胎长骨骺板c—los基因转录和表达的影响/马丽英…//卫生研究.一2000,29(2).一106～108 采用体外培养方法研究锌缺乏对小鼠胚胎长骨骺板c—fos基因(c—fos)转录与表达的影响。将孕龄16d的小鼠胚胎长骨体外培养48h(培养基为GBJb),通过免疫组化及原位杂交方法观察培养长骨骺板c—fos转录与表达的变化,并用图像分析系统对结果进行分析。根据培养基的锌浓度将实验分为对照组、缺锌组、缺锌补锌组、锌刺激量组。结果显示当缺锌时,c—los的蛋白和mRNA表达的减弱,阳性细胞数与对照组相比明显降低(P相似文献   

锌缺乏对培养小鼠胚胎长骨骺板c-fos基因转录和表达的影响

采用体外培养方法研究锌缺乏对小鼠胚胎长骨骺板ｃ－ｆｏｓ基因（ｃ－ｆｏｓ）转录与表达的影响。将孕龄１６天的小鼠胚胎长骨体外培养４８小时（培养基为ＧＢＪｂ）,通过免疫组化及原位杂交方法观察培养长骨ｃ－ｆｏｓｌ转录与表达的变化,并用图像分析系统对结果进行分析。根据培养基的锌浓度将实验分为对照组,缺锌组,缺锌补锌组,锌刺激量组。     

锌对生长期大鼠海马Uch-L1表达的调控作用

目的探讨锌对生长期大鼠海马Uch-L1表达水平的调控作用。方法雄性断乳Wistar大鼠36只,按体重随机分为对照组(ZA)、缺锌组(ZD)和缺锌对喂组(PF),ZD组喂饲含锌量1.5mg/kg的缺锌饲料,PF组和ZA组喂饲含锌量30mg/kg的足锌饲料,PF组摄食量与ZD组一致。喂饲4周后,测定血浆锌含量和碱性磷酸酶活性以评价机体锌状况,用避暗试验测定各组大鼠的学习记忆能力,采用Western blot和RT-PCR方法检测各组大鼠海马Uch-L1蛋白及其mRNA的表达水平。结果ZD组血浆锌含量及碱性磷酸酶活性均显著低于PF组和ZA组;ZD组大鼠在避暗试验中的进洞潜伏期显著低于PF组和ZA组;与PF组和ZA组相比,ZD组大鼠海马Uch-L1及其mRNA表达水平明显降低。结论缺锌可下调大鼠海马Uch-L1表达水平。     

Effects of isolated zinc deficiency on the composition of skeletal muscle, liver and bone during growth in rats

We investigated the effects of zinc deficiency on body composition by using intragastric force-feeding to obviate decreased food intake and altered eating patterns. Weanling male Sprague-Dawley rats were fed a purified zinc-deficient diet: the ad libitum-fed control group (AL; eight rats) was given powdered diet and water containing 25 ppm zinc; the zinc-replete group (ZN; nine rats) was force-fed a diet blended with water containing zinc in an amount of equal caloric intake to the AL group and allowed access to water containing zinc. The zinc intake of ZN rats was approximately twice that of AL rats based on water intake. The zinc-deficient group (ZD; 13 rats) was fed similarly to the ZN group except deionized water was used for diet preparation and drinking water. After 8 d, body and muscle weight were lower in the ZD group than in the ZN group. Femur weights were similar in the two groups. Serum, liver and femur zinc concentrations were 85, 22 and 42% lower, respectively, in the ZD group than in the ZN group. Serum glucose, relative liver weight, liver glycogen and liver lipids were higher, but muscle and liver DNA were lower in the ZD group than in control groups.     

锌缺乏对生长期雄性大鼠海马泛素C末端水解酶L1表达的影响

[目的]观察缺锌对生长期大鼠海马泛素C末端水解酶L1(UCH-L1)表达的影响。[方法]将SD大鼠随机分为正常组、缺锌配喂组和缺锌组,正常组喂饲常锌饲料(32.5mg/kg),缺锌配喂组喂饲高锌饲料(73.5mg/kg),缺锌组喂饲缺锌饲料(1.2mg/kg)。饲养4周后处死动物,取海马组织,RT-PCR法检测UCH-L1mRNA的表达水平,Westernblot法检测UCH-L1蛋白的表达水平。[结果]与正常组和缺锌配喂组比较,缺锌大鼠海马中UCH-L1mRNA和蛋白的表达水平均显著下调。[结论]缺锌大鼠海马UCH-L1的表达异常,可能是缺锌导致认知损伤的重要机制之一。     

Dietary zinc deficiency decreases glutathione S-transferase expression in the rat olfactory epithelium

Zinc deficiency leads to olfactory and gustatory dysfunction, but little is known about the underlying molecular mechanism of this phenomenon. We examined the effect of dietary zinc deficiency on the rat olfactory epithelium. Immunoreactivities of glutathione S-transferase (GST) mu, neuron-specific enolase (NSE) and proliferating cell nuclear antigen (PCNA), and in situ hybridization of GST mu mRNA in the olfactory epithelia were examined under different dietary zinc intake conditions. Adult male rats were fed a zinc-deficient (ZD) diet (0.5 mg zinc/kg diet), whereas control rats, including pair-fed (PF) and zinc-adequate (ad libitum consumption, AL) groups, were fed a zinc-adequate diet (58 mg zinc/kg diet) for 7 wk. We also examined the effect of zinc replacement (ZR) by subsequently feeding half of the ZD group a zinc-adequate diet for 5 wk after the initial 7-wk deprivation. No significant differences in immunoreactivity for NSE in olfactory epithelial receptor cells or for PCNA in basal cells were noted among groups. Intense GST mu immunoreactivity and hybridization signals were observed in olfactory supporting cells of AL, PF and ZR groups, but very minimal or no such signal was noted in ZD rats. Our findings indicated that zinc deficiency reduces GST mu expression in the supporting cells of rat olfactory epithelia but does not affect receptor cell proliferation or maintenance.     

Zinc supplementation of pregnant rats with adequate zinc nutriture suppresses immune functions in their offspring

The knowledge about consequences of marginal zinc (Zn) deficiency and Zn supplementation during pregnancy on immune function in the offspring is limited. The aim of this study was to examine whether effects of mild Zn deficiency and subsequent Zn supplementation during pregnancy persist after weaning and affect immune function of the offspring. Adult female rats were fed a Zn-adequate diet (ZC, n = 8) or a Zn-deficient diet (ZD, n = 8) from preconception through lactation. Pregnant rats were supplemented with either Zn (1.5 mg Zn in water) or placebo (water) 3 times/wk throughout pregnancy. Pups were orally immunized with cholera toxin and bovine serum albumin-dinitrophenol (DNP) 3 times at weekly intervals and killed 1 wk after the last dose. Proliferation and cytokine responses in lymphocytes from Payer's patches and spleen, and antigen specific antibodies in serum were studied. Zn supplementation of ZD dams led to enhanced lymphocyte proliferation and IFN-gamma responses in pups ZDZ+. In contrast, Zn supplementation of ZC dams suppressed these responses in pups ZCZ+. Total and DNP-specific IgA responses were lower in pups of the Zn-deficient group compared with the Zn-adequate group. Relative thymus weight was greater in the pups (ZDZ-) of ZD placebo-supplemented dams compared with the other groups at 31 d of age. Prepregnancy and early in utero Zn deficiency affected IgA responses in pups that could not be restored with Zn supplementation during pregnancy. Zn supplementation of ZC dams induced immunosuppressive effects in utero that may also be mediated through milk and persist in the offspring after weaning.     

Expression of the mouse metallothionein-I and -II genes provides a reproductive advantage during maternal dietary zinc deficiency.

The function of metallothionein in zinc homeostasis was examined by using mice homozygous for knockout (KO) of the metallothionein-I or -II (MT-I and MT-II) genes. Pregnant MT-I/II KO mice or control mice were fed a zinc-deficient (1 microg/g or 5 microg/g) diet or a zinc-adequate (50 microg/g) diet during specific periods of pregnancy, and the effects on morphogenesis of the embryos were determined at day 14 of pregnancy (day 1 = vaginal plug). In the homozygous MT-I/II KO, as well as in the nontransgenic control mice, severe dietary zinc deficiency (1 microg/g) beginning on day 1 of pregnancy was embryotoxic and teratogenic, and the majority of the embryos in both strains were dead by mid-gestation. However, 53% of the surviving embryos in the MT-I/II KO mice were morphologically abnormal compared to only 32% of the embryos in the control mice. In subsequent experiments, moderate dietary zinc deficiency (5 microg/g beginning on day 1 of pregnancy or 1 microg/g dietary zinc beginning on day 8 of pregnancy) exerted teratogenic, but not embryotoxic effects. Embryos in the MT-I/II KO mice were 260 to 290% as likely to develop abnormally than were embryos in the control mice fed these same diets. These results demonstrate that the expression of the MT-I and -II genes in pregnant females improves reproductive success during maternal dietary zinc deficiency.     

Moderate zinc deficiency reduces testicular Zip6 and Zip10 abundance and impairs spermatogenesis in mice

Male infertility accounts for ~40% of cases of failure to conceive. Testes have a strict zinc (Zn) requirement and severe Zn deficiency compromises spermatogenesis, sperm viability, and motility, compromising fertility in men. Despite the high prevalence of marginal Zn deficiency in humans, less emphasis has been placed on understanding the consequences on male reproduction. Swiss Webster mice were used to visualize Zip protein expression during spermatogenesis using immunohistochemistry. Data suggest Zip5 imports Zn into Sertoli cells and spermatocytes, augmented by Zip10 (primary spermatocytes) and Zip8 (secondary spermatocytes). Zip6, 8, and 10 expression was retained in round spermatids, although Zip8 and Zip10 expression disappears during spermatid maturation. Zip1 and Zip6 expression was detected in mature, elongated spermatids. Zip14 was detected in undifferentiated spermatogonia and Leydig cells. Mice fed diets (n = 10/group) reduced in Zn concentration [marginal-Zn diet (MZD), 10 mg Zn/kg; low-Zn diet (ZD), 7 mg Zn/kg] for 30 d had >35% lower liver Zn concentrations than mice fed the control diet (C; 30 mg Zn/kg) (P < 0.05). Plasma Zn and testosterone concentrations and the testes Zn concentration and weight were not significantly lower than in controls. Plasma Zn was greater in the ZD group than in the C and MZD groups. Mice fed ZD had a reduced number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells (~50%; P < 0.05), compromised seminiferous tubule structure, and reduced Zip10 and Zip6 abundance (>50%; P < 0.5) compared with mice fed C. Our data provide compelling evidence that reduced Zn intake may be associated with infertility in men, perhaps independent of decreased levels of circulating Zn or testosterone, which warrants further investigation in human populations.