钙,锌对小鼠肝金属硫蛋白合成及肝锌,钙水平的影响

同时经口给小鼠喂饲锌盐（１００ｍｇ／ｋｇ，锌）和钙盐（０～１６０ｍｇ／ｋｇ，钙），观察钙、锌对小鼠肝金属硫蛋白（ＭＴ）合成及肝锌、钙水平的影响。结果表明喂饲的钙剂量较高（≥４０ｍｇ／ｋｇ）时，小鼠肝ＭＴ的含量与钙剂量呈明显的负相关，，而肝锌和钙的含量均没有发生明显的变化。     

锌诱导金属硫蛋白体内合成的实验研究

对孕兔皮下注射氯化锌溶液，探讨了不同浓度的氯化锌对孕兔肝脏和胚胎金属硫蛋白（ＭＴ）合成的影响。实验结果表明，低剂量的氯化锌２ｍｇ／ｄ（每公斤体重），能诱导兔肝内金属硫蛋白的合成增多，当每天给孕兔注射氯化锌２０ｍｇ／ｄ（每公斤体重）时，兔肝脏金属硫蛋白的合成可高出对照组８．３倍，胚胎内金属硫蛋白水平也有明显的升高，提示母体锌水平不但影响自身肝脏金属硫蛋白的合成，而且可影响胚胎金属硫蛋白的水平。     

乙醇对铁过载大鼠肝细胞脂质过氧化和胶原代谢的影响

目的：研究乙醇对铁过载大鼠肝原代细胞脂质过氧化反应和胶原合成的影响。探讨铁和乙醇在诱导肝细胞脂质过氧化反应时的相互关系，以及脂质过氧化反应对胶原合成的影响。方法：在饲料中添加３％（ｗ／ｗ）的Ｃａｒｂｏｎｙｌｉｒｏｎ造成铁过载动物模型，从铁过载大鼠和正常大鼠中分离来的肝原代细胞与不同浓度的乙醇（０、２５、５０、１００ｍｍｏｌ／Ｌ）及０．５ｍｍｏｌ／Ｌ去铁敏（ｄｅｓｆｅｒｏｘａｍｉｎｅ）共同培养２４小时。测定肝组织和细胞中铁含量，肝细胞成活率，肝细胞中脂质过氧化产物丙二醛（ＭＤＡ），还原型谷胱甘肽（ＧＳＨ）、羟脯氨酸含量。结果：铁过载组肝细胞铁含量明显高于对照组，而从铁过载组分离来的肝细胞随乙醇剂量的增加细胞中ＭＤＡ、羟脯氨酸含量增加、ＧＳＨ含量下降，加入０．５ｍｍｏｌ／Ｌ去铁敏可有效地抑制此变化。结论：铁和乙醇在诱导肝细胞脂质过氧化反应时存在协同作用，肝细胞内铁含量增高可增加乙醇的肝细胞毒性，铁和乙醇诱导的脂质过氧化反应／产物可刺激肝细胞胶原的合成     

锌诱导小鼠肝产生金属硫蛋白的实验研究

给小鼠腹腔注射Ｚｎ盐,应用镉饱和法测定肝金属硫蛋白的量。结果显示：连续３天给小鼠低于致死量的锌盐与其诱导产生肝ＭＴ的量间存在时间－效应、剂量－效应关系。     

四种锌化合物的生物利用率的比较

目的：以边缘性锌缺乏的大鼠和幼鼠为模型，观察硫酸锌、葡萄糖酸锌、乳酸锌和甘氨酸锌四种锌化合物在０～７２０分钟消化吸收的动态变化；四种锌化合物在不同剂量（７．６、１５、３０、６０ｍｇ／ｋｇＨ２Ｏ）时组织中的储存。结果：以相同浓度的锌灌胃（６．０ｍｇ／ｋｇｂｗ），甘氨酸锌入血快于其它三个锌化合物，在１５分钟时达到最高峰（１００μｍｏｌ／Ｌ），乳酸锌和葡萄糖酸锌３０ｍｇ／ｋｇ时吸收峰值最大（６６．０μｍｏｌ／Ｌ，７９．５μｍｏｌ／Ｌ）；硫酸锌则在６０分钟到达高峰（７８．９μｍｏｌ／Ｌ）。用不同剂量锌（１５、３０、６０ｍｇ／ｋｇＨ２Ｏ）喂养幼鼠，甘氨酸锌在１５ｍｇ／ｋｇ、乳酸锌和葡萄糖酸锌３０ｍｇ／ｋｇ时血和组织中吸收峰值最大，且成直线关系；而３０、６０ｍｇ／ｋｇ时血和组织中浓度则基本保持恒定。而硫酸锌的吸收与剂量浓度关系成正比。以硫酸锌的吸收为１００％，用药物代谢动力学软件３Ｐ８７计算葡萄糖酸锌、乳酸锌和甘氨酸锌相对生物利用率分别为：１３２％、７３％和１２４％。     

缺锌和补锌对大鼠血清锌、铜及血脂水平影响的研究

健康雄性Ｗｉｓｔａｒ大鼠４５只，先进行２５天锌缺乏实验，继之２１只大鼠再进行１５天锌补充实验。结果显示，缺锌可致大鼠血清总胆固醇（ＴＣ）及低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）含量增高，而血清锌（Ｚｎ）、高密度脂蛋白胆固醇（ＨＤＬ－Ｃ）及其亚组分ＨＤＬ２－Ｃ含量明显下降，并且血清Ｚｎ含量与上述各指标均呈很好的剂量反应关系。适量补锌（１２ｍｇ／ｋｇ和３０ｍｇ／ｋｇ）均可使大鼠的各项指标完全恢复，而大剂量补锌（２５０ｍｇ／ｋｇ）则使ＨＤＬ－Ｃ及ＨＤＬ２－Ｃ有延迟恢复的趋向。血清铜（Ｃｕ）含量始终无明显改变。提示，膳食锌含量缺乏可致血脂代谢紊乱，而大剂量补锌又可使血脂恢复延迟，因此，膳食中Ｚｎ含量应有适当的剂量范围。     

甲醛染毒大鼠脂质过氧化水平分析

用不同剂量（５，１０，２０，５０，１００ｍｇ／ｋｇ）甲醛经腹腔注射染毒ＳＤ大鼠后２４小时，以及１０ｍｇ／ｋｇ染毒后２，６，２４小时收集大鼠血和肝脏。对样品的测定结果显示，红细胞ＳＯＤ活性，全血ＧＳＨ－ＰＸ活性，红细胞内谷胱甘肽含量以及血浆与肝组织ＭＤＡ浓度等五项指标与染毒剂量均有不同程度相关，其中红细胞ＳＯＤ对甲醛最为敏感，５ｍｇ／ｋｇ时就比对照组有明显降低，在时间效应关系中可以见到红细胞内ＳＯＤ     

枸杞总黄酮类化合物抗脂质过氧化研究

利用Ｆｅ２＋－Ｃｙｓ－Ｈｉｓ体系诱发鼠肝线粒体和红细胞产生脂质过氧化的方法,研究了枸杞总黄酮类化合物（ＴＦＬ）的抗脂质过氧化作用。结果表明,ＴＦＬ可阻断该体系诱发的鼠肝线粒体脂质过氧化,当ＴＦＬ终浓度在０．０２５～２．０ｍｇ／ｍｌ范围时,对丙二醛（ＭＤＡ）生成阻断率为３８．３８％～９９．９６％,呈剂量－效应关系,同时具有保持线粒体膜流动性的作用。扫描电镜观察到ＴＦＬ对脂质过氧化所致红细胞形态结构的破坏有保护作用。     

枸札总黄酮类化合物抗脂质过氧化研究

利用Ｆｅ＾２＋－Ｃｙｓ－Ｈｉｓ体系诱发鼠肝线粒体和红细胞产生脂质过氧化的方法,研究了枸札总黄类化合物（ＴＦＬ）的抗脂质过氧化作用。结果表明,ＴＦＬ可阻断该体系发的鼠肝线粒体脂质过氧化,当ＴＦＬ终浓度在０．０２５－２．０ｍｇ／ｍｌ范围时,对丙二醛（ＭＤＡ）生成阻断率为３８．３８％－９９．９６％,呈剂量－效应关系,同时具有保持线粒体膜流动性的作用、扫描电镜观察到ＴＦＬ对脂质过氧化所致红细胞形态结构的皮     

矽宁在人体内的药代动力学研究

建立了高效液相色谱法测定人体全血中矽宁浓度。该法最低检测浓度为０．０１ｍｇ／Ｌ，平均回收率为９６．３％±０．４％，日内及日间的精密度（ＣＶ）分别为５．９％及８．９％。全血中矽宁浓度在０．０４～１２００ｍｇ／Ｌ时呈良好的线性关系。健康男性志愿者７名，口服单剂量矽宁１００ｍｇ后，其药代动力学过程符合二室一次吸收模型。该药在消化道内吸收较快，滞后时间为０．１８８ｈ，血浆浓度达峰时间为０．６９５ｈ，全血消除相半衰期（Ｔ）为６．２６３ｈ，表现分布容积为０．３ｍＬ／ｋｇ。     

Dietary zinc deficiency and repletion modulate metallothionein immunolocalization and concentration in small intestine and liver of rats

Metallothionein (MT) functions in zinc (Zn) homeostasis and dietary Zn affects tissue MT concentration. The objective of this study was to investigate the effects of dietary Zn deficiency and 24-h Zn repletion on MT immunolocalization and concentration in the small intestine and liver of growing rats. Three-week-old rats fed Zn-deficient diet (< 1 mg Zn/kg) for 16 d had no MT staining in either small intestine or liver. After 24-h Zn repletion with control diet (30 mg Zn/kg), strong MT staining was observed in intestinal Paneth cells and surface epithelial cells in the proliferative regions of villi. Pair-fed control rats had strong MT staining in liver that was localized around central veins. After 24-h energy repletion, the hepatic MT staining diminished. Furthermore, Zn-deficient rats had significantly reduced intestinal (57%) and hepatic (61%) MT concentrations but unaffected Zn concentrations compared with controls that consumed food ad libitum. Zn repletion for 24 h restored intestinal and hepatic MT concentrations and reduced hepatic Zn concentration. Pair-fed control rats had elevated MT concentration in liver that was normalized by energy repletion. There was a significant positive correlation between tissue Zn and MT concentrations in liver (r = 0.60, P = 0.0001), but not in small intestine. In summary, MT immunolocalization and concentration in rat small intestine and liver were responsive to changes in Zn status, supporting the role of MT in Zn metabolism. Cell-type-specific localization of MT in small intestine after dietary Zn manipulations indicates a function of Zn and MT in gut immunity and intestinal mucosal turnover, and the pattern of hepatic MT distribution with energy restriction may be linked to detoxification processes.     

Pharmacological zinc and phytase supplementation enhance metallothionein mRNA abundance and protein concentration in newly weaned pigs

The swine industry feeds pharmacological zinc (Zn) to newly weaned pigs to improve health. Because most swine diets are plant-based with a high phytic acid content, we hypothesized that adding phytase to diets could reduce the amount of Zn required to obtain beneficial responses. The role of metallothionein (MT) in Zn homeostasis could be important in this positive response. Thus, the goal of this study was to investigate the effect of dietary Zn and phytase on relative MT mRNA abundance and protein concentration in newly weaned pigs. Diets containing adequate (150 mg Zn/kg) or pharmacological concentrations of Zn (1000 or 2000 mg Zn/kg), as zinc oxide, with or without phytase [0, 500 phytase units (FTU)/kg, Natuphos, BASF] were fed in a 3 x 2 factorial design. Plasma and tissue minerals were measured in pigs killed after 14 d of dietary intervention. Hepatic and renal relative MT mRNA abundance and protein were greater (P < 0.05) in pigs fed 1000 mg Zn/kg with phytase, or 2000 mg Zn/kg with or without phytase vs. the remaining treatments. Intestinal mucosa MT mRNA abundance and protein were greater (P < 0.05) in pigs fed 2000 mg Zn/kg with phytase than in pigs fed 2000 mg Zn/kg alone or 1000 mg Zn/kg with phytase. Pigs fed 1000 mg Zn/kg plus phytase or 2000 mg Zn/kg with or without phytase had higher plasma, hepatic, and renal Zn than those fed the adequate Zn diets or 1000 mg Zn/kg. We conclude that feeding 1000 mg Zn/kg with phytase enhances MT mRNA abundance and protein and Zn absorption to the same degree as 2000 mg Zn/kg with and without phytase.     

The effects of zinc deficiency on turnover of cadmium-metallothionein in rat liver

The object of this experiment was to determine the effects of Zn deficiency on the turnover of Cd-induced metallothionein (MT) in rat liver. Male rats were fed a purified Zn-deficient or Zn-adequate diet. After 13 days, the rats were given three daily injections of Cd2+ totaling 1.5 or 3.0 (Zn-deficient) and 3.0 or 6.0 (Zn-adequate) mg Cd/kg body weight. The MT was labeled by injecting the rats with [35S]cystine 2 hours after the final Cd injection. One, 3 or 5 days after labeling, the rats were killed, and their livers were assayed for MT 35S and metal content. The metal composition of MT (mole %) was 41-42% Cd, 51-54% Zn and 4-7% Cu in the Zn-adequate groups and 64% Cd, 27-31% Zn and 6-9% Cu in the Zn-deficient groups. The half-lives of Cd-induced MT in the Zn-deficient rats were 2.6 days (1.5 mg Cd/kg) and 2.8 days (3.0 mg Cd/kg). In the Zn-adequate rats, the half-lives were 3.6 days (3.0 mg Cd/kg) and 3.1 days (6.0 mg Cd/kg). The half-lives of general, soluble hepatic proteins were 4.1 to 4.3 days in all groups. Despite the stabilizing effect of the higher Cd content, the half-life of hepatic MT in the Zn-deficient rats was significantly shorter than in the Zn-adequate rats. These results indicate that hepatic MT degradation is faster in Zn-deficient animals.     

Metallothionein in mice reduces intestinal zinc loss during acute endotoxin inflammation, but not during starvation or dietary zinc restriction

Normal metallothionein [(MT)+/+] and MT-null (MT-/-) mice were used to examine the influence of MT on Zn retention and the metabolic consequences of 2 d food deprivation, with and without inflammation induced by intraperitoneal injection of bacterial endotoxin lipopolysaccharide (LPS). LPS reduced fecal Zn concentration in MT+/+ mice from 5.9 +/- 0.2 micromol/g on d 1 to 2.2 +/- 0.2 micromol/g on d 2, but not in MT-/- mice, 5.9 +/- 0.2 and 5.7 +/- 0. 5 micromol/g, respectively. MT+/+ mice fed an 8 mg Zn/kg diet and injected with LPS excreted 40% less Zn over 2 d than their MT-/- counterparts. Starvation for 2 d did not lower fecal Zn concentration in either genotype, although in MT+/+ mice, urinary Zn excretion was reduced from 12.7 +/- 1.3 nmol on d 1 to 5.9 +/- 1.8 nmol on d 2 and plasma Zn concentration was lowered to 9.8 +/- 0.4 micromol/L. Zn was not reduced in urine or plasma of MT-/- mice, with respective values of 10.8 +/- 2.0 nmol on d 1, 9.3 +/- 2.9 nmol on d 2 and 13.0 +/- 1.0 micromol/L. LPS injection resulted in much higher total liver Zn (677 +/- 27 nmol) and MT (106 +/- 2 nmol Cd bound/g) than starvation (Zn = 405 +/- 21, MT = 9 +/- 3) in MT+/+ mice after 2 d, but did not further reduce urinary Zn. LPS-injected MT-/- mice had no rise in liver Zn or fall in plasma and urine Zn. MT-/- mice fed a Zn-deficient (0.8 mg Zn/kg) diet lost 10% of body weight over 25 d compared with no loss in MT+/+ mice. Despite this, MT-/- mice excreted no more Zn via the gut than did MT+/+ mice. In summary, MT inhibits intestinal Zn loss when highly expressed. When uninduced, typically during Zn deficiency, MT appears to conserve Zn and body mass by reducing only urinary and other nonintestinal Zn losses.     

Comparative study of effect of acute administration of cadmium and silver on ceruloplasmin and metallothionein: Involvement of disposition of copper,iron, and zinc

Male ICR mice were subcutaneously injected with either aqueous Ag (1.5 or 5.0 mg/kg) or Cd (1.5 or 2.5 mg/kg) for 2 consecutive days. Body fluids and livers were collected 24 hr after the second dose. In the hepatic supernatant, Ag and Cd were recovered at 2 and 36–46% of the total dose, respectively. Ag-metallothionein (MT), which is associated with Ag, Cu, and Zn, and Cd-MT, which is associated with Cd, Cu, and Zn, were induced in the liver by the injection of Ag and Cd, respectively. The supernatant Ag and Cd existed in the MT fraction at 34–61 and 97% levels, respectively. Cu concentration in the hepatic supernatant was increased by the Ag and Cd injections. The increased Cu was due to the appearance of Ag-MT and Cd-MT, respectively. Microsomal concentrations of Cu increased in the Cd groups, but decreased in the Ag groups. Serum ceruloplasmin (Cp) activity was remarkably increased by the injection of Cd, but severely decreased by the injection of Ag. These opposing changes in Cp activity induced by Cd and Ag may be due not to the sequestering of Cu in MT, but to the alteration of microsomal Cu concentration and/or the difference in affinity of the induction metals to MT. Hepatic Fe concentration was increased by the Ag injection, but was decreased by the Cd injection. These changes may not be related to induction of MT, but to Cp synthesis in the liver.     

Metallothionein-null mice absorb less Zn from an egg-white diet, but a similar amount from solutions, although with altered intertissue Zn distribution

The influence of metallothionein (MT) on Zn transfer into non-gut tissues was investigated in MT-null (MT-/-) and normal (MT+/+) mice 4 h after oral gavage of aqueous 65ZnSO4solution at doses of 154, 385, 770 and 1540 nmol Zn per mouse. Zn transfer was not significantly different between MT+/+ and MT-/- mice and was directly proportional to the oral dose (slope = 0.127, r = 0.991; 0. 146, r = 0.994, respectively). Blood 65Zn and plasma Zn concentrations increased progressively in MT-/- mice at doses >154 nmol Zn, reaching levels of 2.4% of oral dose and 60 micromol/L, respectively, at the 1540 nmol Zn dose. The corresponding values for MT+/+ mice were approximately half, 1.0% and 29 micromol/L. Intergenotypic differences were found in tissue distribution of 65Zn within the body; MT-/- mice had higher 65Zn levels in muscle, skin, heart and brain, whereas MT+/+ mice retained progressively more Zn in the liver, in conjunction with a linear increase in hepatic MT up to the highest Zn dose. MT induction in the small intestine reached its maximum at an oral dose of 385 nmol Zn and did not differ at higher doses. Absorption of a 770 nmol 65Zn dose from a solid egg-white diet was only one fourth (MT+/+) and one eighth (MT-/-) of the Zn absorption from the same dose of 65Zn in aqueous solution. MT+/+ mice had greater (P < 0.05) Zn absorption from the egg-white diet than did MT-/- mice, indicating that gut MT confers an absorptive advantage, but only when Zn is incorporated into solid food.     

Iron-induced metallothionein in chick liver: a rapid, route-dependent effect independent of zinc status

The induction of hepatic metallothionein (MT) by the parenteral administration of iron was studied. Iron administered to chicks by intravenous or subcutaneous injection caused a 1.9-fold increase in hepatic MT. In marked contrast, intraperitoneal (ip) Fe resulted in a 10-fold increase, thus demonstrating the importance of the route of metal administration. This route-dependent effect was found to be dose-dependent, with ip injections between 1 and 10 mg Fe/kg resulting in a linear increase in MT and a concomitant reduction in serum zinc concentration and feed intake. High ip doses of Fe resulted in a persistent depression in serum Zn and elevated MT and MTmRNA. Equimolar ip injections of either Zn or Fe showed similar patterns of MTmRNA accumulation. In both cases MTmRNA levels were elevated by 3 h, with a peak at 6 h postinjection (Fe 8-fold, Zn 12-fold above 0 h). Plasma Zn was maximally reduced by Fe at 9 h (60%). The MT induction by Fe, as well as related depression in plasma Zn, was completely inhibited by actinomycin D. Zn depletion eliminated the accumulation of hepatic Zn and MT protein following ip injection of Fe or endotoxin, but not of cadmium, despite marked elevation of hepatic MTmRNA. Our results demonstrate Fe injected into the body cavity of chicks results in a rapid induction of hepatic MT that, like endotoxin induction, is independent of dietary Zn status.     

褪黑素降低亚硒酸钠对小鼠的肝毒性

目的研究褪黑素对亚硒酸钠致小鼠肝毒性的影响。方法 30只雄性昆明小鼠(体重18~20 g),随机分为3组,每组10只。对照组,每日灌胃生理盐水;亚硒酸钠组和亚硒酸钠+褪黑素组,每日灌胃亚硒酸钠6 mg/kg bw。2 h后,对照组和亚硒酸钠组灌胃2%的乙醇水溶液;亚硒酸钠+褪黑素组,灌胃褪黑素15 mg/kg bw(溶解在2%的乙醇水溶液)。连续6 d。检测小鼠血清转氨酶,肝脏丙二醛含量,总抗氧化能力,超氧化物歧化酶和过氧化氢酶活力、及肝脏谷胱甘肽过氧化物酶和谷胱甘肽硫转移酶活力,研究褪黑素对亚硒酸钠致肝毒性、氧化应激和调节含硒酶和二相酶的影响。结果与结论褪黑素可以减轻毒性剂量亚硒酸钠产生的氧化应激,降低亚硒酸钠的毒性,且不降低其预防癌症的疗效。     

高锌日粮对蛋鸡生产性能和蛋锌含量影响的研究

４０周龄伊莎蛋鸡２００只，随机分为４组，分别饲喂基础日粮（Ｉ组），添加锌１００ｍｇ／ｋｇ（Ⅱ组），１０００ｍｇ／ｋｇ（Ⅲ组）和酵母锌４０ｍｇ／ｋｇ（Ⅳ组）。饲喂６０日后，Ｉ组、Ⅱ组、Ⅲ组和Ⅳ组鸡蛋中的锌含量分别为１０．６１、１８．３１，２１．２７和２３．７１μｇ／ｇ。Ⅱ组产蛋率明显上升（Ｐ＜０．０５），破壳率明显下降（Ｐ＜０．０５）；Ⅲ组和Ⅳ组产蛋率显著增加（Ｐ＜０．０１），玻壳率和料蛋比显著下降（Ｐ＜０．０１），同时试验鸡无异常表现，解剖后组织器官也无病理变化，实验表明，通过对蛋鸡饲喂高锌日粮增加蛋中的锌含量效果显著。