Delayed plasma clearance and hepatic uptake of lymph chylomicron 14C-cholesterol in marginally zinc-deficient rats

Previously, chylomicrons from marginally zinc-deficient rats were shown to be abnormally large, with markedly reduced levels of apoproteins C and E. In the present study, effects of such changes on the plasma clearance and hepatic uptake of chylomicron cholesterol were investigated in rats fed 3 ppm of zinc (ZD), as compared with those fed 30 ppm of zinc (CT). The rate of plasma clearance was determined by plasma 14C-radioactivity at different intervals after intravenous injection of lymph chylomicrons labeled in vivo with 14C-cholesterol. The 14C-clearance curves were nonlinear, consisting of an initial rapid phase followed by a slow phase of clearance. The initial 14C-clearance was significantly (p less than 0.05) delayed whether the labeled chylomicrons from ZD donors were injected into ZD or CT recipients. The hepatic 14C-recovery in extracted lipids was also significantly lower in ZD rats. The present data provide first evidence that a marginal level of zinc deficiency produces a significant delay in the plasma clearance and hepatic uptake of chylomicron cholesterol. This may be attributable in part to the molecular alterations of chylomicrons induced by zinc deficiency.     

缺锌对生长期大鼠行为及海马细胞钙状态的影响

为探讨缺镜对生长期大鼠行为以及海马细胞内游离钙([Ca^2 ])和活性钙调素（CaM)水平的影响。选用21只雄性Wi star大鼠，随机分为缺锌组，对喂组，对照组，缺锌组组饲以缺锌饲料，对喂和对照组饲以普通饲料，喂饲3周后，用旷场试验进行为行为测定，之后处死大鼠，分别用Fura-2双波长荧光法和流式细胞术测定动物海马细胞[(Ca^2 ])i和活性CaM水平。结果表明，缺锌组组大鼠在旷场内的行为与对照组出现明显差异，其海马细胞[Ca^2 ]i明显高于对照和对喂组，缺锌组和对喂组大鼠海马细胞活性CaM水平均明显低于对照组，缺锌组组大鼠细胞活性CaM水平也明显低于对喂组，缺锌对生长期大鼠行为的影响可能与其影响海马神经元的钙状态有关。     

Zinc deficiency suppresses the development of oral tolerance in rats

Oral tolerance is a specific immune unresponsiveness to food antigens to prevent hypersensitivity reactions. We investigated whether zinc deficiency affects oral tolerance. Rats were fed a control (C) or zinc-deficient (ZD) diet, or pair-fed (PF) to ZD rats for 28 d. Beginning on d 7, rats were administered ovalbumin (OVA) orally to induce tolerance, or PBS 3 times/wk, and were then immunized by OVA injection. The proliferation of mesenteric lymph node (MLN) and spleen lymphocytes after in vitro OVA stimulation and the delayed-type hypersensitivity were higher in OVA-fed ZD than in OVA-fed C rats and not different between OVA- and PBS-fed ZD rats, indicating a suppression of tolerance. Lymphocyte proliferation did not differ between PF and C rats. Expressions of cytokines involved in oral tolerance, i.e., interleukin (IL)-4, IL-10 and transforming growth factor-beta, were higher in OVA- than in PBS-fed C rats, but not in ZD rats. Apoptosis was higher in OVA- than in PBS-fed C rats but not different between OVA- and PBS-fed ZD rats. Inflammation and ulcerations that were not present in ZD rats on d 7 (ZD(7)) developed in OVA- or PBS-fed ZD rats. Compared with ZD(7) rats, tumor necrosis factor-alpha and cytokine-induced neutrophil chemoattractant were higher in OVA- and PBS-fed ZD rats, whereas interferon-gamma increased only in OVA-fed ZD rats. In conclusion, zinc deficiency suppresses oral tolerance through dysregulation of cytokine expression and lack of antigen-specific clonal deletion. We suggest that abrogation of tolerance may lead to development of mucosal inflammation and damage.     

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。     

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。     

Reevaluation of zinc deficiency on concanavalin-A-induced rat spleen lymphocyte proliferation

Zinc concentrations of serum, nonlymphoid and lymphoid tissues, and the responsiveness of concanavalin-A (Con-A)-stimulated spleen lymphocytes (SL) and cervical lymph node cells ( CLNC ) from ad libitum-fed zinc-deficient (ZD), pair-fed (PF) and ad libitum-fed zinc-adequate rats (AL) were determined. In vitro effects of serum from ZD, PF and AL rats on responsiveness of Con-A-stimulated SL and CLNC were determined. Weanling male Long-Evans rats were fed ad libitum zinc-deficient (less than 1.0 microgram Zn/g diet) and zinc-adequate (20 micrograms Zn/g diet) diets for 7-42 days. Effects of undernutrition on test parameters were determined on PF rats, which received a restricted zinc-adequate diet (restricted in amount to that consumed by ZD rats). Growth, food intake and zinc concentrations in serum, liver and pancreas were significantly depressed in ZD and PF rats. Zinc per gram of thymus tissue and per number of SL was elevated in ZD and PF rats. Spleen lymphocytes from ZD and PF rats displayed equivalent to significantly increased levels of proliferation following stimulation with Con-A. [3H]Thymidine incorporation by Con-A-stimulated SL and CLNC from ZD, PF and AL rats was not significantly different when cultured in medium containing serum from ZD, PF and AL rats. The present study shows that zinc deficiency causes major changes in total-body and organ growth but minor changes in zinc content and mitogen-induced proliferation of lymphocytes.     

Noradrenergic activity in the paraventricular nucleus and macronutrient choice during early dark onset by zinc deficient rats

Carbohydrate is a preferred macronutrient of rats during the early dark phase and associated with an increase in norepinephrine (NE) and neuropeptide Y (NPY) in the paraventricular nucleus (PVN). Macronutrient choice is altered during zinc deficiency (ZD). The relationship between NE activity in the PVN and macronutrient choice during early dark was evaluated in rats fed zinc adequate (ZA) or ZD diet for 14 days. Total caloric intake was similar for ZA and ZD groups (-20 kJ) but ZA rats selected 63 +/- 5% of calories as carbohydrate while ZD rats selected 53 +/- 5% of their calories from protein (p < 0.01). Pair-fed (PF) rats selected 62 +/- 5% of calories as carbohydrate. Noradrenergic activity was lower (p < 0.01) in ZD and PF compared to ZA. The association between increased NE in the PVN at dark onset and selection of carbohydrate is not supported by the present results.     

The absorption of pteroylpolyglutamate and intestinal pteroylpolygammaglutamyl hydrolase activity in zinc-deficient rats

The effect of dietary zinc deficiency on pteroylpolygammaglutamyl hydrolase (folate hydrolase) activity and on pteroylpolyglutamate absorption was studied in rats. Three groups of male Sprague-Dawley rats (zinc-deficient, restricted-fed and ad libitum-fed controls) were fed a semipurified 25% egg white protein diet. The zinc-deficient group received 0.7 mg zinc/kg diet, whereas restricted-fed and ad libitum-fed control groups received 106 mg zinc/kg diet. After 6 wk of feeding, intestinal mucosal folate hydrolase activity was determined, and the absorption of pteryl-U[14C]glutamylhexaglutamic acid [(14C]PteGlu7) and [3H]pteroylglutamic acid [(3H]PteGlu) was measured after intragastric administration. The intestinal mucosal folate hydrolase activity of zinc-deficient rats was not significantly reduced compared with two control groups. No significant differences in the absorption of [14C]PteGlu7 and [3H]PteGlu were found among the three groups. These results indicate that intestinal folate hydrolase is not zinc dependent in rats and the intestinal absorption of pteroylpolyglutamate is not reduced in zinc-deficient rats.     

心理应激时大鼠海马神经元的钙状态变化及锌的作用研究

目的 :　研究不同锌营养水平的大鼠在应激条件下的行为变化 ,观察海马细胞内游离钙 ([Ca2 + ]i)及活性钙调素 (Ca M)水平改变 ,以探讨其可能机制。方法 :　大鼠按体重随机分为缺锌组 (ZD)、缺锌应激组 (SZD) ,对喂组 (PF)、对喂应激组 (SPF) ,对照组 (CT)、对照应激组(SCT)。实验进行 1 w后 ,各应激组大鼠接受不规则光 -电刺激 ,2 5 min/ d连续 1 5 d后进行行为测定 ;分别用 Fura-2 / AM双波长荧光法和流式细胞术测定动物海马细胞 [Ca2 + ]i和活性 Ca M水平。结果 :　单纯缺锌大鼠在旷场中的中央格停留时间延长 ,修饰次数减少 ,海马细胞静息 [Ca2 + ]i浓度升高而 Ca M水平下降 ;与相应非应激组比较 ,各应激组大鼠在旷场中的水平和垂直运动减少 ,海马细胞 [Ca2 + ]i含量升高 ,以缺锌应激组最为明显 ;活性钙调素水平则呈相反变化。结论 :　光电应激导致实验大鼠在旷场中行为异常 ,并因机体缺锌而加重 ;推测海马细胞内 Ca2 + -Ca M体系的变化可能是其机制之一     

Zinc status affects neurotransmitter activity in the paraventricular nucleus of rats

Alterations in neurochemical activity in the paraventricular nucleus (PVN) of the hypothalamus may account for decreased intake of zinc-deficient diets. Male Sprague-Dawley rats were fed zinc-deficient (ZD) or zinc-adequate (ZA) diet for 14 d before samples of extracellular fluid in the PVN were collected by microdialysis or push-pull perfusion. A third set of rats was pair-fed (PF) an amount of ZA diet equal to the intake of ZD rats. Samples were collected over a 2-h period spanning the transition from light to dark. All rats then consumed the zinc adequate diet ad libitum for 3 d before a second set of samples was collected. The increase in extracellular norepineprhrine (NE) during h 1 of the dark period to 147 +/- 13% of baseline (P < 0.05) was apparent only in ZA rats at d 14. After the 3-d repletion period, the increase in NE at dark onset occurred in all three groups. An increase in extracellular neuropeptide Y (NPY) at dark onset to 174 +/- 32% of baseline in rats fed ZA (P < 0.01) was measured in all three groups at both d 14 and 17. Basal NPY concentrations were significantly elevated in PF rats on d 14 (7.45 +/- 2.01 vs. 0.58 +/- 0.23 pmol/L, P = 0.01) and returned to ZA levels by d 17. The activities of the NE and NPY systems in the PVN were altered in rats fed a zinc-deficient diet; however, it is unclear whether the disruption in the NE and NPY neural systems in the PVN results in the altered feeding behavior accompanying zinc deficiency.     

缺锌对生长大鼠学习记忆功能及生长状况的影响

目的 :　研究缺锌对大鼠生长、学习和记忆功能的影响。方法 :　进行了三系列实验 ,第 1、2系列分组均为缺锌组 (ZD)、对喂组 (PF)和缺锌补锌组 (ZS) ,但第 1系列饲养期为 35d,缺锌补锌组缺锌 2 1 d后补锌 ;第 2系列饲养期 2 8d;第 3系列分组为缺锌组、对喂组和自由采食组(AL) ,饲养期 2 8d,全程观察生长过程 ,定期称重 ,并于实验结束前 1 w内用避暗法测定各组大鼠的学习和记忆功能。结果 :　三次实验均表明 ,ZD组大鼠生长、学习和记忆功能降低 ,而补锌后 ,则能逆转上述状况。结论 :　锌不仅影响生长 ,且与学习和记忆等脑的高级功能有关     

Cholesterol and apolipoprotein distribution in plasma high-density-lipoprotein subclasses from zinc-deficient rats

Effect of zinc deficiency on the composition of plasma high-density-lipoprotein (HDL) subclasses was investigated in adult male rats (ZD) fed a diet containing 2.8 micrograms of Zn/g as compared with pair-fed (PF) and ad libitum-fed (CT) controls given 30.8 micrograms of Zn/g. Three HDL subclasses were isolated by heparin-affinity chromatography: HDL containing no apo E (HDL-E0), HDL with a moderate amount of apo E (HDL-E1), and HDL highly enriched in apo E (HDL-E2). The plasma levels of total HDL cholesterol and protein were markedly decreased in ZD. The decreases were due primarily to a significant decline in circulating HDL-E0 particles. The percent content of free cholesterol in HDL-E2 was increased in ZD compared with PF and CT. Zn deficiency decreased the plasma concentrations of apo A-I and apo C of HDL-E0 and total apo E associated with HDL-E1 and HDL-E2. The mechanisms for such changes await further investigation.     

生长期大鼠缺锌时股骨病理形态学的改变

目的　通过建立生长期缺锌大鼠模型以阐明锌缺乏对生长期儿童骨骼发育的影响 ,为儿童生长发育迟缓的防治提供理论依据。方法　刚断奶的雄性大鼠随机分为对照组 (ZA)、缺锌组 (ZD)、配饲组 (PF) 3组 ,每组 10只。喂养 15天后处死 ,取股骨称量重量及测量长度、直径 ,并做病理组织切片 ,观察股骨病理改变。结果　ZD组股骨长度 [(2 4 . 80± 0 . 4 2 )mm]明显低于PF组 [(2 6 . 70± 0 . 4 8)mm]及ZA组 [(2 7. 90± 0 . 32 )mm](P <0 . 0 1) ;ZD组股骨直径 [(2 . 0 9± 0 .0 9)mm]明显低于PF组 [(2 . 70± 0 . 0 8)mm]及ZA组 [(2 . 80± 0 . 0 8)mm](P <0 . 0 1) ;ZD组股骨重量 [(0 .5 1± 0 . 0 5 )g]明显低于PF组 [(0 . 6 5± 0 . 0 8) ]及ZA组 [(0 . 76± 0 . 10 )g](P<0 . 0 1)。缺锌组大鼠股骨骺生长板软骨细胞畸形、数量减少 ,骺端骨小梁纤细、疏松、排列紊乱、髓腔相对扩大 ,骨小梁体积显著减少 ,骨小梁板密度降低 ,骨小梁间隙增大。结论　生长期动物缺锌可导致骨骼的形态及病理发生改变而影响骨骼的生长发育。     

Studies of marginal zinc deprivation in rhesus monkeys: II. Pregnancy outcome

A marginal state of zinc deficiency was induced in the pregnant nonhuman primate, Macaca mulatta, by feeding a diet containing 4 ppm zinc beginning at conception. Pregnancy outcome of marginally zinc-deficient monkeys (ZD) was compared to both pair-fed (PF) and ad libitum fed (AL) control animals (100 ppm zinc). Stillbirths, abortions, and delivery complications were more frequent in both ZD and PF dams than in AL controls; no malformations were detected (maternal plasma zinc was normal during organogenesis). Male ZD neonates weighed significantly less than same sex controls; also, in relation to colony norms, 7/8 ZD males, 2/8 ZD females, and 1/10 PF controls were of low birth weight. Further, plasma zinc and iron levels were lower in ZD neonates than in AL and PF controls. ZD neonates also had reduced muscle tonus. Birth weight and maternal plasma zinc concentration were negatively correlated in ZD group but positively correlated in AL and PF groups. Indeed, maternal plasma zinc concentration alone did not identify a state of zinc deficiency which impaired fetal growth in monkeys.     

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。     

Cholesterol transport in mesenteric lymph of the preruminant calf: contribution of cholesterol transposition from blood to lymph

Eight preruminant male calves were prepared surgically with lymphatico-venous shunts and re-entrant gallbladder to proximal duodenum shunts. Liquid diets were formulated to contain 12.5% dried skim milk (SM) or 10.5% SM to which was added 2% soybean oil (SBO), milk fat (MF) or beef tallow (T). Two calves were assigned to each dietary treatment. Transposition of cholesterol from blood capillaries to intestinal lymph was determined by injection of 100 microCi [4-14C]-cholesterol into the blood of calves at feeding time. To avoid recirculation of [4-14C]-cholesterol via the enterohepatic circulation, bile was diverted and replaced with bile from a donor calf fed an identical diet. For the SM, SBO, MF and T diets, respectively, cholesterol transposed from capillaries was 44, 61, 36 and 48% of the cholesterol transported in the mesenteric lymph. When cholesterol synthesis in response to test diets was calculated, we found that intestinal cholesterol synthesis is less when calves are fed SM or SBO than when fed T or MF.     

Reduced growth and skeletal changes in zinc-deficient growing rats are due to impaired growth plate activity and inanition

We investigated the effects of dietary zinc deficiency on skeletal metabolism in an animal model. Thirty 21-d-old male Sprague-Dawley rats were fed for 28 d either a zinc-deficient (ZD) diet (1 mg zinc/kg) or a normal diet ad libitum (AL, 50 mg zinc/kg) or in the same quantity as the ZD (pair-fed, PF). Only in the ZD group were general physical signs of zinc deficiency observed. Compared with the AL and PF rats, ZD rats showed significantly lower mean values in ponderal growth rate, femur weight and length, circulating levels of insulin-like growth factor-I, bone mechanical properties and concentration of zinc and, on histomorphometry, a decrease in the thicknesses of the overall growth plate and hypertrophic cartilage. In contrast, although bone volume was significantly lower in the ZD and PF rats than in the AL rats, no difference was observed between the ZD and PF rats. Osteoclast surface/bone surface and osteoclast number/bone surface ratios were significantly greater in PF rats than in the other two groups and not different in ZD and AL rats. Collectively, these data indicate that zinc deficiency has profound effects on the skeletal system of growing rats. In particular, the effects of zinc deficiency on bone growth and mass are the result of the reduced activity of the growth plate, likely mediated by impairment in the insulin-like growth factor-I system. We did not demonstrate an effect on bone mass via increased bone resorption.     

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...     

The rate of rhodopsin regeneration in the bleached eyes of zinc-deficient rats in the dark

Rats fed a zinc-deficient, phytate-containing diet (ZD rats) for 4 wk showed typical signs of zinc deficiency: reduced food intake, slow weight gain, a poor food efficiency ratio and subnormal zinc concentrations in the serum, femur and eye. Pair-fed, weight-matched rats fed a zinc-sufficient diet (PF rats) showed normal serum zinc values, intermediate femur zinc levels and eye zinc concentrations similar to those in ZD rats. The vitamin A status of all three groups, expressed as the concentration of vitamin A in the liver, was comparable. After extensive bleaching, the initial rate of rhodopsin regeneration in ad libitum-fed, zinc-sufficient rats (AL rats), ZD rats and PF rats was the same, whereas the extent of rhodopsin regeneration in AL rats kept in the dark for 120 min was almost twice that found in ZD and PF rats. These results are not consistent with the hypothesis that zinc deficiency primarily affects dark adaptation by reducing the activity of alcohol dehydrogenase in the eye. Rather, zinc deficiency and the generalized malnutrition that results from markedly reduced food intake seem to depress the synthesis of opsin, and probably other proteins as well, in the rod cells of the eye.     

Influence of reduced food intake on polyunsaturated fatty acid metabolism in zinc-deficient rats

The influence of reduced food intake on metabolism of liver phospholipids (PL) in zinc-deficient (ZD) rats was measured. Wealing male Long-Evans rats were fed ad libitum zinc-deficient (2 micrograms Zn/g diet) and zinc-adequate (20 micrograms Zn/g diet) diets for 21 days. A pair-fed (PF) group was included. ZD and PF rats displayed significantly increased levels of linoleic (18:2 omega 6) and dihomo-gamma-linolenic acid (20:3 omega 6). Both ZD and PF rats displayed increased levels of gamma-linolenic acid (18:3 omega 6), but the increase was significant only in PF rats. ZD and PF rats displayed decreased levels of arachidonic acid (20:4 omega 6), but the decrease was significant only in PF rats. Both ZD and PF rats displayed significantly reduced levels of 22:5 omega 6. Both ZD and PF rats displayed increased products of delta 6 desaturation and decreased products of delta 5 and delta 4 desaturation. Significantly increased products of delta 9 desaturation were noted in both ZD and PF rats. ZD and PF rats displayed significant increases in C20 elongation products. ZD and PF rats displayed significantly decreased levels of omega 6 metabolites but not total omega 6 acids. ZD rats showed significantly increased levels of total omega 3 acids and omega 3 metabolites. ZD and PF rats showed significant increases in omega 9 acids but not significant changes in omega 9 metabolites. This study does not indicate that zinc affects the delta 6 desaturase in the metabolism of essential fatty acids. The aberrations previously attributed to zinc deficiency are probably due to the accompanying decreased food intake.