补充微量营养素减轻应激损伤的实验研究

目的　观察复合微量营养素对大鼠应激损伤的预防作用。方法　按低、中、高 3种剂量给实验大鼠补充含有维生素、氨基酸和矿物元素的复合营养素 ,以间断足底电击建立动物应激模型 ,检测其旷场行为、应激反应、应激蛋白及抗氧化功能的变化。结果　足底电击诱导的应激反应引起实验大鼠行为异常改变 ,血浆皮质醇浓度升高 ,脑组织儿茶酚胺含量减少。应激动物肝脏和脑组织中的金属硫蛋白含量出现不同程度的变化 ,同时血清总抗氧化能力降低而肝组织脂质过氧化物水平增加。补充 6周微量营养素的应激大鼠行为异常得到逆转 ,上述血液和组织的多数生化指标也出现明显改善。结论　补充复合微量营养素有利于提高实验动物的应激适应能力 ,减轻机体的应激反应损伤     

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。     

锌营养对大鼠应激反应及金属硫蛋白的影响

目的：在心理应激条件下，观察大鼠组织中金属硫蛋白（MT）水平的变化及其与锌营养状况的关系。方法：60只雄性Wistar大鼠随机分为6组：缺锌组（ZD）、喂对组（PF）、对照组（CT），以及相应的3个应激组（SZ、SP、SC）。以光－电刺激方法建立心理应激动物模型，观察应激对皮质醇激素、锌和金属硫蛋白的影响。结果：应激诱导动物脑和肝脏MT含量增加，而血浆锌出现不同程度下降。缺锌动物血锌浓度降低，肝脏和脑中金属硫蛋白的含量减少，而其整体应激反应强度增加。结论：维持良好的锌营养状况有助于诱导整体和脑组织产生应激蛋白，并提高机体对心理应激的适应能力。     

胰脏的金属硫蛋白防止镉对胰岛素分泌的抑制

本研究试图证实:投给小鼠镉后,胰脏中是否能检出金属硫蛋白。实验结果表明:腹腔注射醋酸镉后,在很短时间内胰脏就出现金属硫蛋白。有人认为金属硫蛋白是先在胰脏周围的另一器官合成,然后被运至胰脏,认为肝脏的可能性最大。可是,胰脏出现此种蛋白的速度和浓度却否定此种可能性。Probst等(1977)曾发现:注射镉后约3小时,肝脏尚未开始合成金属硫蛋白;而在本研究中,给镉后1.5小时,即能在胰脏内检出一定量的金属硫蛋白。因     

乙醇对大鼠脑、肝金属硫蛋白浓度的影响

目的 研究长期乙醇摄入对神经中枢系统的影响，探讨酒精中毒致服损伤的机理。方法 Wistar大鼠每天经灌胃染毒0，10％，30％，50％浓度的乙醇0．5ml，持续2个月。用原子吸收法检测大鼠脑、肝等组织中锌、铜含量；血红蛋白饱和法测金属硫蛋白的含量。结果 长期乙醇摄入后，大鼠脑、肝等组织中金属硫蛋白水平呈上升趋势。雄性大鼠以50％乙醇剂量组的上升效应最明显，大服、小脑、海马、肝、肾中金属硫蛋白水平分别为对照组的2．27，1．53，1．45，1．22，2．58倍（P＜0．05）；雌性大鼠在30％乙醇剂量组上升效应最显，大脑、小脑、海马、肝、肾中金属硫蛋白水平分别为对照组的1．39，3．08，1．75，1．49，1．46倍（P＜0．05）。另外，长期乙醇摄入后，大鼠脑、肝等组织中锌、铜含量均发生明显变化，金属硫蛋白与锌含量的变化呈现明显相关。结论 长期摄入乙醇可诱导大鼠脑、肝金属硫蛋白含量增加，且存在性别差异。     

不同方式给铝对大鼠体内金属硫蛋白诱导作用的初步研究

目的研究体内铝与金属硫蛋白的关系。方法１６只ＳＤ大鼠按实验和对照两种剂量水平，通过皮下注射和灌胃两种给铝方式进行为期两周的铝对金属硫蛋白（ＭＴ）诱导实验。结果铝对大鼠肝ＭＴ具有一定的诱导作用，其中以皮下注射方式给铝较经口方式的作用显著。经口给铝对小肠也存在一定诱导作用。结论铝对ＭＴ的诱导体现了机体对铝这一金属毒物的应激反应，但由于铝的化学性质，推测其与ＭＴ结合不稳定，因此这一反应实际解毒作用尚不确定。此外铝对小肠和肝等不同部位ＭＴ的诱导，可能会影响锌等金属元素的正常代谢     

在小白鼠肝金属硫蛋白合成中钙和锌的相互影响

在小白鼠肝金属硫蛋白合成中钙和锌的相互影响杨森，戴建国，陈景衡金属硫蛋白（ＭＴ）是一种结合金属的低分子量蛋白质，分子量大约７０００，半胱氨酸含量约占总氨基酸的３０％，不含芳香族氨基酸，具有明显的热稳定性。ＭＴ与金属的代谢和解毒有关，ＭＴ对镉和其它非必...     

锌疗法与酒精性肝病

研究证实,酒精性肝病的发生与肝组织中锌离子及其主要结合蛋白-金属硫蛋白的减少存在相关性。动物实验研究显示,补锌疗法可以用于预防处于急、慢性酒精暴露条件下所引起的肝损伤。补锌疗法可以保护消化道粘膜的完整性和预防内毒素血症的发生,由此避免了肝脏中内毒素诱导的肿瘤坏死因子-α生成。锌也可以直接阻止内毒素诱导的肿瘤坏死因子-α产生的信号途径。锌的这些肝内和肝外作用是不依赖金属硫蛋白的。然而,当金属硫蛋白过低时肝脏更易于发生酒精性损伤,并且当体内发生氧化应激时,高水平的金属硫蛋白可增强内源性锌离子的储存和释放。在预防和治疗酒精性肝病方面,锌可能成为一种高潜能的有效制剂。     

发育过程中肝脏铜的储存及运输：细胞毒性作用（二）

肝细胞内铜大多与特异性金属结合蛋白结合，主要有谷胱甘肽，血浆铜蓝蛋白以及金属麦硫因。肝细胞内金属麦硫因及铜含量的变化在整个个体发育过程中具有重要意义、金属麦硫因能提供铜的暂时性储存并且能防止它成为具人毒性作用的金属自由基，因此其在对抗铜细胞毒性的作用。     

镉对大鼠骨髓锌、铜、铁含量的影响

实验动物给予镉后,在蓄积金属的器官可诱导金属硫蛋白的生成,特别是肝脏和肾脏。这种金属硫蛋白也可导致锌和铜在组织的潴留。因为镉的蓄积可引起锌和铜内环境稳定的明显改变,结果使得其他生化过程中金属的效能减低,并可能引起组织衰竭。已知慢性镉接触可使肝脏铁的贮存降低,以及血浆中金属含量的减少。在其他毒性方面,长期接触镉可产     

应激对缺锌和补锌大鼠脂质过氧化的影响

以电击和束缚两种方式建立动物应激模型，观察应激因素对缺锌和补锌大鼠脂质过氧化的影响。结果表明，无论接受电击或束缚应激，缺锌大鼠血浆及肝脏ＬＰＯ含量均显著升高（Ｐ＜０．０１），亦高于补锌动物；接受电击的大鼠肝脏ＭＴ含量显著增加（Ｐ＜０．０１），补锌后增加更明显。结果提示，电击或束缚应激可增强大鼠的脂质过氧化反应，补锌可减轻其应激性氧化损伤     

不全饥饿对大鼠组织中微量元素及金属硫蛋白代谢改变的影响

建立不全饥饿大鼠模型，观察其组织中Ｚｎ、Ｃｕ 等微量元素及金属硫蛋白的代谢改变。结果表明：不全饥饿组动物体重及附睾脂肪垫重量明显低于正常组；而肝、肾及脑组织中Ｍ Ｔ 含量显著增高。提示不全饥饿可诱导组织ＭＴ 合成，有利于减轻机体过氧化损伤。     

锌对小鼠肝金属硫蛋白合成的影响

本文研究了小鼠在宽的剂量范用内（１０，２０，４０，８０，１００，１２０，１４０，１６０，１８０，２００ｍｇ／ｋｇｂｗ）口服锌（Ｚｎ）盐时，对肝金属硫蛋白（ＭＴ）合成的影响。结果显示：因服用过量Ｚｎ（２＋），按剂量──效应关系发生肝ＭＴ的诱导合成，而且在肝Ｚｎ浓度和肝ＭＴ浓度之间存在正向关系。表明Ｚｎ是一个ＭＴ的诱导剂。在口服Ｚｎ８０～１００ｍｇ／ｋｇ的剂量范围时，无论是肝ＭＴ水平或肝Ｚｎ水平均有明显的改变。提示：在Ｚｎ诱导ＭＴ合成中，存在一个敏感的剂量范围。     

金属硫蛋白在动物体内的功能及其基因表达调控

金属硫蛋白(metallothioneins,MTs)是一类富含金属和巯基的低分子量蛋白质,在动物体内金属元素的代谢、清除自由基、应激防护等方面发挥重要作用。MT基因的表达是通过MT基因启动子上的几种反应元件由许多生化介质引发的。综述了MT在动物体内的功能及其基因表达的调控作用及主要机制。     

Photoperiod affects hepatic and renal cadmium accumulation, metallothionein induction, and cadmium toxicity in the wild bank vole (Clethrionomys glareolus)

The objective of this study was to examine the toxic effects of dietary cadmium (Cd) on bank voles, being the F1 offspring of a wild-caught population. For 6 weeks, the rodents were provided with diets containing 0.05 (control), 40, 80, and 120 microg Cd/g dry wt of diet under moderate (12 h) and long (16 h) photoperiods. Histological examinations and analyses of metallothionein (MT), Cd, Cd bound and not bound to MT, iron and lipid peroxidation in the liver and kidneys were carried out. Histopathological changes occurred in the liver (infiltrations of leukocytes) and kidneys (hemorrhage, glomerular injury, tubular cell degeneration) of bank voles fed the highest dose of dietary Cd only under the moderate photoperiod. The same voles also exhibited the highest values of hepatic and renal Cd, Cd not bound to MT, and renal lipid peroxidation. It seems that under the long photoperiod the liver and kidneys of bank voles were protected against Cd-induced injury through decreasing Cd accumulation and increasing synthesis of MT.     

Chronic vitamin E inadequacy and thermally treated oils affect the synthesis of hepatic metallothionein isoforms

Summary Background: Metallothionein (MT)^# synthesis can be stimulated in many organs not only by various metals such as cadmium, zinc, and copper, but also by many nonmetalic compounds or experimental conditions such as oxidative stress. The latter lead to the hypothesis that MT is induced in response to free radicals formed in tissues and lipid peroxidation. Aims of the study: Whether the relationship between lipid peroxidation amd MT synthesis is a common phenomenon also valid for lipid peroxidation induced by dietary factors such as chronic vitamin E inadequacy and autoxidation products of polyenoic fatty acids derived from thermally oxidized oil was investigated in the presence study. Methods: The relationship between the induction of metallothionein isoforms I and II (MT-I and MT-II) in response to diet-induced lipid peroxidation using a rat model system in which lipid peroxidation was examined in vivo by chronic vitamin E inadequacy or by administration of lipid peroxidation products from a thermally treated polyenoicrich oil with either basal (dietary zinc concentration: 48 mg/kd; experiment 1) or Zn-stimulated MT levels (dietary zinc concentration: 305 mg/kd; experiment 2) was studied. In both experiments, growing male rats were fed diet containing either a fresh or a thermally treated soybean oil with deficient of sufficient amounts of vitamin E (14 and 11 vs. 648 and 560 mg α-tocopherol equivalents per kg diet) over 40 days according to a bifactorial experimental design. Plasma and liver concentrations of tocopherols and hepatic levels of thiobarbituric acid-reacitve substances (TBARS) were measured by high performance liquid chromatography. MT isoform concentrations in rat liver were isolated and quantified by ion-exchange high performance liquid chromatography and atomic absorption spectrometry. Results: Irrespective of the zinc supply, rats receiving inadequate amounts of vitamin E with the diet had markedly lower plasma and liver concentrations of α-tocopherol and total tocopherols than vitamin E-sufficient rats. ANOVA also revealed an interaction between the diet factors vitamin E and oil on tocopherols in plasma and liver of rats from both experiments. In experiment 1, where rats received normal amounts of dietary zinc, ingestion of the thermally treated oil impaired the tocopherol status compared to the treatment with the fresh oil, although this effect was only obvious in the vitamin E-deficient groups. In experiment 2, where rats received excessive amounts of zinc, the thermally treated oil did not contribute to a reduction of the tocopherol status in plasma and liver. In both experiments a significant increase in TBARS level, indicative of lipid peroxidation, was observed in the liver at chronic vitamin E inadequacy, but no effect of the oil was observed. Here, we show that the dietary treatment had some effects on the synthesis of liver metallothionein isoforms. In groups, receiving normal amounts of zinc, there was a significant interaction between the dietary treatments on the levels of MT-I and MT-II in liver. Chronic vitamin E inadequacy which was accompanied by diminisched tocopherol levels in liver induced the synthesis of MT-I and MT-II. When vitamin E inadequacy was combined with the ingestion of a thermally treated polyenoic acid-rich oil hepatic levels of MT-I and MT-II remained low. In experiment 2, where rats were fed the high zinc diet, vitamin E inadequacy caused an increase of hepatic MT-I level just as in experiment 1, although this MT stimulating effect was irrespective of the oil. For MT-II there was a 43% increase in the vitamin E-deficient group fed the fresh oil compared to all the other groups, although this effect was not statistically significant. The liver MT isoform response to stress was similar in rats with basal MT levels and Zn-induced liver MT levels. The failing effect of the thermally treated oil on MT levels which were stimulated by vitamin E deficiency in experiment 2 was possibly due to the low oxidation grade of the thermally treated oil. Conclusion: The present results are strongly indicative of an apparent induction of MT isoform synthesis in response to an impaired antioxidant defence system in the lipid regions of liver cells induced by vitamin E inadequacy. In contrast, thermally treated polyenoic-rich oils with a certain oxidation grade seem to restrain the induction of MT isoform synthesis under the present experimental conditions. Received: 10 January 2000, Accepted: 27 April 2000     

Effect of lead on ALA-D activity,metallothionein levels,and lipid peroxidation in blood,kidney, and liver of the toadfish Halobatrachus didactylus

The effects of lead (Pb) on ALA-D activity, metallothionein (MT) levels, and lipid peroxidation in liver, kidney, and blood of the toadfish Halobatrachus didactylus were investigated. A time-course experiment was performed with sampling on days 0, 2, 5, and 7 following intraperitoneal Pb injection. This indicated a rank order for lead concentration of kidney > liver > blood in fish exposed to Pb. No significant variation of ALA-D activity was observed in liver and kidney while in blood, a slight decrease of ALA-D activity was found but this was not attributed to acute metal stress. Hepatic and renal MT levels were both affected in different ways by metal uptake. The progressive decrease of MDA concentration in the liver and the lack of a clear induction in kidney suggested the hypothesis that Pb is not a good inductor of lipid peroxidation. The histological and histochemical results demonstrated degenerative effects of lead accumulation on the tissues and the activation of lysosomal responses to induced stress.