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。     

母体锌向胎体转运的初步探讨

本研究通过肌注氯化锌的动物实验，主要进行锌通过胎盘屏障和血脑屏障从母体转运到胎体的研究。实验采用原子吸收法测定母体和胎体组织中锌、铜、铁的含量，用ＳｅｐｈａｄｅｘＧ－７５柱分析法测定金属硫蛋白（ＭＴ）的含量。结果表明，经皮下注射的无机锌，能迅速经母血转运到母体的肝脏、肌肉及胎盘，实验组与对照组之间差别显著，不同孕期的实验组间锌含量无显著性差异。在早孕阶段，锌能通过胎盘屏障转运到胚胎，实验组和对照组问有显著的差异（Ｐ＜０．０１），中孕阶段，实验组胎脑中的锌含量比对照组也有增高的趋势。母体肝脏和胚胎ＭＴ的合成受锌的诱导，实验组胚胎ＭＴ（０．４６ｎｍｏｌ／ｇ）约是对照组（０．１０ｎｍｏｌ／ｇ）的４．５倍。推测ＭＴ在锌的转运中起重要作用。     

甘草甜素和齐墩果酸对大鼠镉中毒性肝损伤的防护作用与机理

为探讨甘草甜素（ＧＬ）和齐墩果酸（ＯＡ）对大鼠镉中毒性肝损伤的防护作用及其作用机理,给大鼠腹腔注射ＣｄＣｌ２溶液（０．８ｍｇＣｄ＾２＋／ｋｇ体重）,两组染镉大鼠分别同时皮下注射ＧＬ的生理盐水溶液（２０ｍｇ／ｋｇ,每周３次）和ＯＡ的吐温－生理盐水混悬液（６０ｍｇ／ｋｇ,每周５次）,测定血清转氨酶、肝镉（Ｃｄ）、金属硫蛋白（ＭＴ）含量,检查肝组织病理形态学。结果显示：ＧＬ和ＯＡ延缓、降低了镉引起的血清     

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。     

锌对镉所致胚胎毒性的保护作用研究

实验用Ｗｉｓｔａｒ大鼠，分为正常组、低锌组、低锌染镉组、正常染镉组和染镉高锌保护组，分别饲养，其中三组在孕８和１０天注射镉（２．０ｍｇ／ｋｇ）。妊娠第２０天处死动物，取血，并剖腹检查孕鼠内脏和胎鼠畸形情况。研究发现：与正常对照组相比，单纯缺锌即可引起胎鼠的吸收率增高和畸形的发生；而染镉（２．０ｍｇ／ｋｇ）也可引起胎鼠的吸收胎和迟死胎显著增加，并可引起皮下水肿、卷尾等外观畸形。在孕期缺锌的同时，给予孕鼠２．０ｍｇ／ｋｇ体重的镉，孕鼠在整个孕期体重呈负增长，胚胎不能形成；如给予孕鼠高锌饲养（２２７ｍｇ／ｋｇ），胎鼠可得到较好的保护，其吸收胎、死胎率明显下降，存活率显著上升，且胎鼠体重、身长也与对照组相差无几。提示孕鼠缺锌可引发胎儿畸形，缺锌染镉加重胚胎毒作用，而高锌膳食能拮抗镉所造成的胚胎毒作用。     

钴毒性的剂量效应

急性：一个１９月龄男性幼儿摄入约３０ｍｌ氯化钴溶液，尽管在半小时内给予灌洗和支持治疗，但数小时后死亡。 慢性：Ｒｏｎｃｏｖｉｔｅ是一种钴一铁药物，以前用于治疗难治性贫血。每日给予５０ｍｇ～１００ｍｇ氯化钴（１８．５ｍｇ／ｄ～３７ｍｇ／ｄ的钴量）的此制剂，机体可长期耐受无明显毒性。给一组孕妇每日摄入７５ｍｇ～１００ｍｇ氯化钴后，出现血红蛋白水平轻度降低，但未发现其它毒性反应。有镰状细胞的儿童每公斤体重口服３ｍｇ～４ｍｇ氯化钴引起甲状腺肿效应，停止治疗后消退。发生心肌病的饮啤酒者的估计每日摄入量为６…     

孕兔接触镉对胎仔肝脏金属硫蛋白的诱导

对金属硫蛋白的研究表明:胎仔一如母体也可产生金属硫蛋白,而且它与锌的贮存和调节有关。本文作者进一步研究了镉对孕兔及胎仔的毒作用(体重、肝、肾、胎盘等脏器重量及体长)、在亚细胞器的分布、金属硫蛋白的产生及其中镉、锌含量的变化。孕兔处死前48小时皮下一次分别注射氯化镉0、0.125、0.25和0.50 mg/kg,纯度99.999%(由于1.0 mg/kg引起胎仔死亡率高,故取消了该剂量组)。结果表明0.50 mg/kg剂量组胎仔的体重、肝重、肾重以及胎仔体长均明显低于对照组(P<0.01)。但其肝脏/体重和肾脏/体重之比未见明显改变。     

谷胱甘肽对含镉金属硫蛋白肾毒性的影响

谷胱甘肽对含镉金属硫蛋白肾毒性的影响欧钢卫，钱民章，葛正龙，任锡麟我们观察了谷胱甘肽（ＧＳＨ）对雄性大鼠含镉金属硫蛋白（ＣｄＭＴ）所引起的类似慢性Ｃｄ中毒肾小管损伤时尿蛋白、尿碱性磷酸酶（ＡＫＰ）、尿Ｃｄ、肾组织金属硫蛋白（ＭＴ）含量的变化，以及肾组...     

砷对小鼠子代生长发育的影响

我们研究了孕鼠接触砷对子代生长发育的影响，结果显示，染砷各组仔鼠机体砷和脑组织砷含量增高，大脑皮层神经细胞结构异常。０．７５ｍｇ／ｋｇ剂量组仔鼠表现为神经行为发育迟缓，外周血淋巴细胞α－醋酸萘酯酶（ＡＮＡＥ）阳性率降低．４．５０ｍｇ／ｋｇ剂量组仔鼠断乳后体重增长缓慢，血液胆碱酯酶活性降低，血清溶血素水平亦显著下降。表明砷可经母体影响胚胎和子代的生长发育。     

混合氨基酸稀土配合物的胚胎毒性研究

在孕鼠“致畸敏感期”分别给予农药混合氨基酸稀土配合物（简称ＭＡＲ）１４２８、７１４、３５７ｍｇ／ｋｇ。１４２８ｍｍ／ｋｍ组胎鼠体重、身长、骨化程度和孕鼠体重增值显著降低，胚胎吸收和胎鼠死亡则增高。提示该剂量ＭＡＲ具有明显胚胎毒性。７１４、３５７ｍｇ／ｋｇ剂量组各项指标与对照组比较则无统计差异。     

Maternal hepatic and embryonic effects of 1,2,4-trichlorobenzene in the rat

The possible maternal hepatic and reproductive effects of 1,2,4-trichlorobenzene (TCB) were assessed in rats given 0, 36, 120, 360, and 1200 mg/kg/day of TCB on Days 9-13 of gestation. The animals were sacrificed on Day 14 of pregnancy. Maternal deaths (2/9 rats, 6/6 rats) were recorded in the 360 and 1200 mg/kg/day treatment groups and body weight gain was significantly decreased in the 360 mg/kg/day TCB group. Maternal liver weight, liver/body weight ratio, and hepatic microsomal protein content were unaffected by TCB treatment. Although Day 14 NADPH-cytochrome c reductase activity was affected only at 360 mg/kg/day TCB, the maternal hepatic microsomal cytochrome P-450 content was significantly increased by administration of both 120 and 360 mg/kg/day of TCB. Hepatic microsomal aminopyrine N-demethylase, ethoxyresorufin O-deethylase, and UDP-glucuronyl transferase activity towards p-nitrophenol were also increased at 120 and 360 mg/kg TCB. Glutathione S-transferase activity to 1-chloro-2,4-dinitrobenzene and 1,2 dichloro-4-nitrobenzene were both increased by pretreatment with TCB. Although pretreatment with 360 mg/kg/day TCB did not increase resorptions, embryolethality, or teratogenicity, embryonic development was significantly retarded by all four growth criteria used (head length, crown-rump length, somite number, and protein content).     

Maternal hepatic effects of 1,2,4,5-tetrachlorobenzene in the rat

1,2,4,5-Tetrachlorobenzene (TCB) is an industrial intermediate used in the production of 2,4,5-trichlorophenoxyacetic acid. This herbicide contains trace quantities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Because of possible maternal hepatic or reproductive effects of this uncharged, low-molecular weight, lipophilic chlorinated benzene 0, 30, 100, 300, and 1000 mg/kg/day of TCB was orally administered to rats on Days 9, 10, 11, 12, and 13 of gestation and the animals were sacrified on Day 14 of pregnancy. No maternal deaths were recorded and body weight gain was significantly decreased only in the 1000 mg/kg/day group. Maternal liver weight, liver to body weight ratio, and hepatic microsomal protein content were unaffected by TCB treatment. Although Day 14 NADPH-cytochrome c reductase activity was not affected, the maternal hepatic microsomal cytochrome P-450 content was significantly increased by administration of 1000 mg/kg/day of TCB. Microsomal N-demethylation of aminopyrine was slightly increased from 2.4 to 3.4 and 3.5 nmole/mg protein/min at doses of 300 and 1000 mg/kg TCB. However, maternal hepatic microsomal ethoxyresorufin O-deethylase activity was greatly increased from 14 to 30, 40, 50, and 49 pmole/mg protein/min in pregnant rats administered 0, 30, 100, 300, and 1000 mg/kg/day TCB. The microsomal rates of p-nitrophenol and phenolphthalein glucuronidation in vitro were not increased by TCB administration. The maternal hepatic microsomal enzyme induction observed after TCB administration to pregnant rats suggests the presence both cytochrome P-450 and P-448 inducers in the sample of 1,2,4,5-tetrachlorobenzene used.     

Effects of gossypol on the estrous cycle and ovarian weight in the rat

The effect of subcutaneously injected gossypol on the estrous cycle and ovarian weights in rats was examined. Daily injections of 5 or 10 mg gossypol/kg/day for 20 days significantly reduced the ovarian weights by 32% and 29%, respectively. Injections of 0.1 and 1.0 mg gossypol/kg/day had no significant effect on ovarian weight. Similarly, ovarian weights were significantly reduced by 37% when hemi-ovariectomized animals were injected with 10 mg gossypol/kg/day for 15 days whereas those of control animals increased in weight by 15%. Animals receiving 5 or 10 mg gossypol/kg/day essentially remained in diestrus by the 15th or the 10th day of injections, respectively. No significant change was found in the liver, adrenal gland or body weight of gossypol-treated rats.     

金属硫蛋白对铬染毒小鼠肝脏氧化损伤的修复作用

目的：探讨金属硫蛋白（MT）对六价铬（Cr6^＋）染毒小鼠肝脏氧化损伤的修复作用。方法：60只清洁级昆明（KM）种小鼠雌雄各半,随机分为5组：对照组,铬（Cr6^＋）染毒组（50mg／kg）,低、中、高（5．0、10．0、20．0mg／kg）剂量MT保护组。对照组灌胃生理盐水,铬染毒组按50nag／（kg·bw）灌胃重铬酸钾溶液;MT保护组在给予铬染毒的同时继续分别按5．0、10．0、20．0mg／（kg·bw）剂量灌胃MT。各组灌胃时间均为15d,每日1次;灌胃体积均为0．1ml／（10g·bw）。实验结束麻醉处死动物采血,取肝脏计算其脏器系数;全自动生化分析仪检测肝功能AST、ALT、GGT含量;试剂盒检测肝组织SOD活性和MDA含量。结果：与对照组比较,铬染毒小鼠体重降低、肝脏器系数增高、血清AST、ALT、GGT增高、SOD活力下降、MDA含量增高（P〈0．05）。经MT保护后与铬染毒组比较小鼠体重有所回升、肝脏脏器系数下降、血清AST、ALT、GGT降低、SoD活力升高、MDA含量下降,其恢复程度与MT呈剂量－效应关系（P〈0．05）。结论：铬（Cr6^＋）对小鼠肝脏有损伤作用,MT对肝脏有保护作用,其机制与抗氧化作用有关。     

Developmental neurotoxicity of chlorpyrifos: what is the vulnerable period?

Previously, we found that exposure of neonatal rats to chlorpyrifos (CPF) produced brain cell damage and loss, with resultant abnormalities of synaptic development. We used the same biomarkers to examine prenatal CPF treatment so as to define the critical period of vulnerability. One group of pregnant rats received CPF (subcutaneous injections in dimethyl sulfoxide vehicle) on gestational days (GD) 17-20, a peak period of neurogenesis; a second group was treated on GD9-12, the period of neural tube formation. In the GD17-20 group, the threshold for a reduction in maternal weight gain was 5 mg/kg/day; at or below that dose, there was no evidence (GD21) of general fetotoxicity as assessed by the number of fetuses or fetal body and tissue weights. Above the threshold, there was brain sparing (reduced body weight with an increase in brain/body weight ratio) and a targeting of the liver (reduced liver/body weight). Indices of cell packing density (DNA per gram of tissue) and cell number (DNA content) similarly showed effects only on the liver; however, there were significant changes in the protein/DNA ratio, an index of cell size, in fetal brain regions at doses as low as 1 mg/kg, below the threshold for inhibition of fetal brain cholinesterase (2 mg/kg). Indices of cholinergic synaptic development showed significant CPF-induced defects but only at doses above the threshold for cholinesterase inhibition. With earlier CPF treatment (GD9-12), there was no evidence of general fetotoxicity or alterations of brain cell development at doses up to the threshold for maternal toxicity (5 mg/kg), assessed on GD17 and GD21; however, augmentation of cholinergic synaptic markers was detected at doses as low as 1 mg/kg. Compared with previous work on postnatal CPF exposure, the effects seen here required doses closer to the threshold for fetal weight loss; this implies a lower vulnerability in the fetal compared with the neonatal brain. Although delayed neurotoxic effects of prenatal CPF may emerge subsequently in development, our results are consistent with the preferential targeting of late developmental events such as gliogenesis, axonogenesis, and synaptogenesis.     

二甲基苯蒽对金属硫蛋白基因敲除小鼠免疫功能的影响

目的：观察二甲基苯蒽（DMBA）对金属硫蛋白（MT）基因敲除小鼠[MT（－／－）]的免疫毒性。方法：选用MT（－／－）小鼠和MT（＋／＋]野生型小鼠进行对照,DMBA25mg/kg和50mg/kg分别1次腹腔注射染毒后,检测动物对静脉注射绵羊红细胞（SRBC）诱导的体液和细胞免疫反应,体液免疫指标为脾脏抗体形成细胞（PFC）数量变化,细胞免疫功能指标选择迟发型变态反应,即动物足跖肿胀厚度变化。结果：DMBA25mg/kg组,MT（－／－）小鼠脾脏和胸腺重量都减轻,体液免疫功能受到抑制（抑制率为72％）,而MT（＋／＋）小鼠仅脾脏重量减轻,两种小鼠的细胞免疫功能均未见明显变化,DMBA50 mg/kg组,MT（－／－）小鼠的体液免疫和细胞免疫功能受到抑制程度均比DMBA25mg/kg组严重（抑制率分别为91％和72％）。MT（＋／＋）小鼠虽脾脏和胸腺重量减轻,体液免疫受到抑制,但变化程度明显小于MT小鼠（－／－）。MT（＋／＋）小鼠没有出现明显的细胞免疫功能抑制。结论：MT（－／－）小鼠的体液免疫和细胞免疫功能更易被DMBA抑制。提示MT具有保护DMBA所致免疫伤的功能。     

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.     

Iron status of suckling rats as influenced by maternal diet during gestation and lactation

1. Two experiments are reported. In Expt 1, pregnant Sprague-Dawley rats (200-220 g) were given purified diets containing 35, 75, 150 or 300 mg Fe/kg throughout gestation and lactation. In Expt 2, the levels of Fe given were 250 and 300 mg/kg diet. 2. Litters were standardized at birth to contain seven pups. On day 20 of lactation blood, milk, spleen and liver were collected for Fe analysis. 3. A dietary Fe concentration of 35 mg/kg maintained maximum weight gain, food intake, liver and spleen weight, haemoglobin concentration and packed cell volume in the growing maternal rat through 20 d of lactation. Dam liver and spleen Fe concentrations were maximized between 75 and 250 mg Fe/kg diet. 4. Pups (20-d-old) nursed by dams given 35 mg Fe/kg tended to have lower body and organ weights compared to other groups. Liver and spleen Fe concentrations increased with increasing maternal dietary Fe and were significantly increased between 150 and 250 mg Fe/kg.