镉,砷及其联合作用对大鼠免疫功能影响的实验研究

本文观察了镉（ＣｄＣｌ_２）、砷（Ａｓ_２Ｏ_３）及其联合作用对大鼠免疫功能的影响。结果表明：持续６周染毒时，见高剂量镉组（４．６８ｍｇ／ｋｇ）对外周血淋巴细胞α－醋酸萘酯酶（ＡＮＡＥ）活性；低剂量砷组（１．３８ｍｇ／ｋｇ）和高剂量砷组（６．９０ｍｇ／ｋｇ）对血清溶菌酶均呈抑制作用。两者联合作用（Ｃｄ低＋Ａｓ低，Ｃｄ高＋Ａｓ高）时，见镉有拮抗砷抑制血清溶菌酶的作用。在三周交替染毒中，发现在单独作用时，高剂量砷组对血清ＩｇＧ和血清溶菌酶的作用均表现为抑制，而低剂量的镉（０．９３７ｍｇ／ｋｇ）则对血清溶菌酶具有兴奋作用。联合作用方面，见在对血清ＩｇＧ和溶菌酶的影响上，镉亦表现出拮抗砷的免疫抑制作用，且先染镉组比后染镉组的作用稍强。     

镓砷和氧化镓肺毒性的比较

作者已报道过ＧａＡｓ对肺与精巢的毒性。本文比较镓的影响,给仑鼠及大鼠气管内反复给与ＧａＡｓ粒子和氧化镓（Ｇａ２Ｏ３）粒子,比较研究通过呼吸道接触各物质的肺毒性。方法：使用８周龄的雄性仑鼠和２周龄的Ｗｉｓｔａｒ雄性大鼠。将其分为ＧａＡｓ组、Ｇａ２Ｏ３组与对照组,仑鼠各组１２只（对照组１１只）,大鼠各组８只。每次投与ＧａＡｓ８．０ｍｇ／ｋｇ（３．９ｍｇＧａ／ｋｇ）,Ｇａ２Ｏ３５．２ｍｇ／ｋｇ,（３．９ｍｇＧａ／ｋｇ）,均悬浮于磷酸缓冲液。向仑鼠及大鼠气管内每周投药２次,计１６次。对照组仅投与磷酸缓冲…     

慢性和急性染镉所致小鼠肾损伤的比较

目的 比较慢性和 性染镉所致肾损伤的差异。方法 给小鼠多次注射ＣｄＣＩ２（剂量：镉０．８￣１．２ｍｇ／ｋｇ，每周６次，共６周），或一次给予大量注射镉金属硫蛋白复合物（ＣｄＭＴ，剂量Ｌ镉０．２￣０．４ｍｇ／ｋｇ），然后比较其肾损伤 。结果小鼠一次性大量注射ＣｄＭＴ主要产生肾脏近曲小管的坏死，虽然其肾镉含量仅为８μｇ／ｇ，但尿蛋白、尿糖、尿酶活力和血尿素氮含量均明显增高。与此相比，慢性染镉的小鼠镉     

四氯化碳诱发大鼠肝损伤对镉肾脏毒性的影响

目的探讨肝损伤对镉肾毒性的影响。方法大鼠腹腔注射ＣｄＣｌ２（含镉０．５ｍｇ／ｋｇ）染毒，第４周末通过灌胃给予ＣＣｌ４９００ｍｇ／ｋｇ，观察大鼠肝、肾功能的变化。结果肝损伤使尿蛋白含量增高和肾小管坏死等肾脏病变提前出现。ＣＣｌ４仅引起一过性的肝损害而未见任何肾功能指标的异常。ＣｄＣｌ２＋ＣＣｌ４联合处理组肾镉临界浓度（７１．５０μｇ／ｇ）明显低于ＣｄＣｌ２组（１００．５５μｇ／ｇ）或ＣＣｌ４＋ＣｄＣｌ２联合处理组（１０３．８０μｇ／ｇ，Ｐ＜０．０５），表明镉染毒大鼠的肝损害能促进镉性肾病的发生和发展，并提高肾脏对镉毒作用的敏感性。结论肝脏功能状态在慢性镉中毒性肾病中起重要的作用。     

N-乙酰半胱氨酸对慢性镉肾毒性的治疗效果

慢性镉的晚期肾毒性目前仍无有效的治疗方法。本研究观察了Ｎ－乙酰半胱氨酸（ＮＡＣ）对镉的肾毒性的治疗效果。选用雌性体重２００～２５０ｇ的大鼠,随机分为对照组和３个实验组,每组６只动物。对照组动物不作任何处理。３个实验组均经皮下注射ＣｄＣｌ２（Ｃｄ）５μｍｏｌ／ｋｇ,每周５次。在Ｃｄ处理第１３周后,其中第１组继续给Ｃｄ至第２０周,第２和第３组从第１４～２２周在继续Ｃｄ处理的同时再经皮下注射ＮＡＣ１００ｍｇ／ｋｇ,每周５次。第２组从第２３周开始停止Ｃｄ和ＮＡＣ的处理。第３组从第２３～２６周再次给予Ｃｄ…     

一氧化氮在急性肝衰竭中的作用

为探讨ＮＯ在急性肝衰竭中的作用，采用Ｄ－ＧａｌＮ（８００ｍｇ／ｋｇ）和ＬＰＳ（８μｇ／鼠）腹腔注射复制大鼠急性肝衰竭模型，用氨胍（ＡＧ，１００ｍｇ·ｋｇ－１·ｄ－１）和左旋精氨酸（ＬＡ，４００ｍｇ·ｋｇ－１·ｄ－１）皮下注射３ｄ，分别抑制和促进ＮＯ的合成，注射Ｄ－ＧａｌＮ和ＬＰＳ后２４ｈ处死，留血清测定ＮＯ、ＡＬＴ和ＡＳＴ的水平，肝组织测定诱导型ＮＯ合酶（ｉＮＯＳ）的活性并作组织学观察。结果发现急性肝衰竭时ＮＯ和ｉＮＯＳ的水平升高（Ｐ＜００５），与ＡＬＴ和ＡＳＴ的升高相一致（Ｐ＜００５），抑制ｉＮＯＳ的活性或促进ＮＯ的合成，则ＮＯ、ＡＬＴ和ＡＳＴ的水平降低（Ｐ＜００５）或升高（Ｐ＜００５），组织学观察证实了上述结果。说明ＮＯ及ｉＮＯＳ参与急性肝衰竭，抑制ＮＯ的合成对急性肝衰竭有保护作用。     

镉对体外培养肾组织中Ca^2＋—APTase对影响及尼莫地 …

目的 探讨镉对镉对组织中Ｃａ＾２＋－ＡＴＰａｓｅ的影响尼尼莫地平（Ｎｉｍｏ）对其的干预作用。方法 在体外条件下,测定ＣｄＣｌ２对肾组织Ｃａ＾２＋－ＡＴＰａｓｅ及乳酸脱氢酶（ＬＤＨ）、碱性磷酸酶（ＡＬＰ）、尿Ｎ－乙酰－Ｄ－氨基葡萄苷酶（ＮＡＧ）等多种肾损伤标志酶活力的作用及Ｎｉｍｏ干预处理后的影响。结果 在低浓度ＣｄＣｌ２组,Ｃａ＾２＋－ＡＴＰａｓｅ的活力明显升高,１００ｍｇ／Ｌ ＣｄＣｌ２组Ｃａ＾     

镉-金属硫蛋白诱发大鼠肾近曲小管细胞凋亡的实验研究

为探讨镉－金属硫蛋白（Ｃｄ－ＭＴ）是否可诱发肾脏细胞的凋亡,首先每天给７周龄雄性Ｗｉｓｔａｒ大鼠皮下注射２ｍｇ／ｋｇＣｄＣｌ２。２周后处死动物,取出肝脏,制备匀浆。１０５０００ｇ离心后取上清液,用ＳｅｐｈａｄｅｘＧ－７５色谱和ＤＥＡＥＡ－２５阳离子交换色谱法提纯,并经混匀、透析和冻干后,制备Ｃｄ－ＭＴ、Ｃｄ－ＭＴ－Ⅰ和Ｃｄ－ＭＴ－Ⅱ的混合物备用。在注射前,将Ｃｄ－ＭＴ－Ⅱ用０．９ＮａＣｌ重新溶解至０．４ｇ／Ｌ。纯化蛋白中镉的含量用电感耦合等离子体原子发射光谱法测定。然后给８周龄大鼠静脉注射Ｃｄ－…     

喹胺酸对急性铍中毒大鼠肝脏损伤的减轻作用

为探讨喹胺酸（ＱＡ）对急性铍中毒的肝脏损伤是否有解毒作用，用Ｗｉｓｔａｒ大鼠由尾静脉注入ＢｅＳＯ４４Ｈ２Ｏ７．５ｍｇ／ｋｇ染毒，继之ＱＡ组大鼠由腹腔注入ＱＡ５００ｍｇ／ｋｇ，以观察ＱＡ的作用；染毒组大鼠注射生理盐水。全部大鼠于染毒前及染毒后第１、３、８天观测肝功能和肝脏病理变化。结果表明：ＱＡ治疗大鼠于染毒后第１天血清ＡＬＴ、ＡＳＴ略有升高，然后逐渐下降，１周内降至正常；染毒组大鼠于染毒后第１天血清ＡＬＴ和ＡＳＴ明显升高，第３天血清ＡＬＴ高达１５００Ｕ／Ｌ，ＡＳＴ６２０Ｕ／Ｌ，血清总胆红素（Ｔ－Ｂｉｌ）３００μｍｏｌ／Ｌ，１周内全部死亡。病理学检查所见：染毒大鼠皮肤黄染，肝脏明显增大，肝细胞肿胀、坏死。ＱＡ治疗大鼠未见明显异常。提示：ＱＡ对可溶性铍急性中毒大鼠肝脏损伤有明显的减轻作用。     

EGE与甲苯和二甲苯联合处理对大鼠EGE代谢和睾丸的影响

男油漆工接触乙二醇乙醚（ＥＧＥ）可引起睾丸萎缩。本研究观察了ＥＧＥ与甲苯和二甲苯联合处理对大鼠睾丸萎缩和血浆中乙氧基乙酸（ＥＡＡ）生成的影响。选用雄性大鼠,体重２５０～３００ｇ。为观察不同剂量ＥＧＥ单独以及与甲苯和二甲苯联合处理对大鼠睾丸的影响,每日经口单独给大鼠ＥＧＥ橄榄油溶液５０、１００、２００、５００和１０００ｍｇ／ｋｇ;同时与甲苯２５０ｍｇ／ｋｇ、二甲苯５００ｍｇ／ｋｇ及甲苯５００ｍｇ／ｋｇ和二甲苯１０００ｍｇ／ｋｇ共同处理;对照组经口给橄榄油０８ｍｌ,每周６次共４周,在最后一次染毒后…     

金属硫蛋白与镉中毒性肝肾损害的关系

目的观察亚慢性镉中毒性肝肾损害,并初步探讨金属硫蛋白（ＭＴ）与肝肾损害的关系。方法用Ｗｉｓｔａｒ大鼠腹腔注射０．５ｍｇ／ｋｇＣｄ２＋的ＣｄＣｌ２３次／周,共１０周,染毒后不同时期处死大鼠,观察肝肾功能变化。结果染毒６周后,大鼠出现了明显的肝肾损害,相应组织中Ｃｄ∶ＭＴ的摩尔数之比均超过７,且随染毒总剂量的增加,Ｃｄ∶ＭＴ值明显增加,病变程度加重。结论肝肾是亚慢性镉中毒的靶器官,非ＭＴ结合的镉可能是损害肝、肾的主要成分。     

Effect of zinc deficiency on the accumulation of metallothionein and cadmium in the rat liver and kidney

The effects of zinc (Zn) deficiency and repeated exposure to cadmium (Cd) on the accumulation and distribution of metallothionein (MT), Cd and Zn in the liver and kidney were studied. Male Sprague-Dawley rats were fed either a Zn-deficient (1 ppm) or a Zn-adequate (40 ppm) diet during the experiment, and the rats were injected subcutaneously with a cadmium chloride solution (1.0 mg Cd/kg of body weight, 5 days a week) for 4 weeks. Cadmium, Zn, and Cd-induced MT concentrations in the liver and kidney were lower in the Zn-deficient rats (–Zn + Cd) than in the Zn-adequate rats (+ Zn + Cd), while the content of Cd bound to high molecular weight proteins (HMWP) was greater in the Zn-deficient rats (–Zn + Cd). The Zn bound to Cd-induced MT was reduced to 30% in the liver and to 60% in the kidney of the Zn-deficient rats (–Zn + Cd) as compared with that of the Zn-adequate rats (+ Zn + Cd). In the kidney of Zn-deficient rats, exposure to Cd caused a decrease in essential Zn associated with HMWP as compared with that of Zn-adequate rats (+ Zn + Cd). Thus, Zn-deficiency affected the distribution of Cd in tissues, MT and HMWP and accelerated substantially Cd-induced Zn-deficiency in the kidney. Although the renal Cd concentration was lower in the Zn-deficient rats (–Zn + Cd) than in the Zn-adequate rats (+ Zn + Cd), exposure to Cd for four weeks resulted in glucosuria and an increase in liver and kidney weights in the Zn-deficient rats (–Zn + Cd), but not in the Zn-adequate rats (+ Zn + Cd). These results suggest that development of Cd toxicity is related to the Zn status of the body, to the accumulation of Cd in HMWP and to the amount of essential Zn associated with HMWP.     

Effects of Picrorrhiza rhizoma water extracts on the subacute liver damages induced by carbon tetrachloride

The hepatoprotective activity of Picrorrhiza rhizoma (PR) water extract was evaluated on carbon tetrachloride (CCl(4))-induced subacute hepatic damage, induced by subcutaneous injection of CCl(4) (0.15 mL/kg of body weight) in pure olive oil (7.92%, vol/vol) three times a week for 10 weeks. Animals were sacrificed 10 weeks after oral administration of PR extracts at 50, 100, or 200 mg/kg or silymarin at 100 mg/kg, which were administered simultaneously with CCl(4); changes in body weight, liver weight, and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were observed along with differences in liver histopathology and histomorphometry. In addition, liver malondialdehyde as an index for lipid peroxidation, hydoxyproline as an index for collagen synthesis, and protein content were determined. Ten weeks of CCl(4) injections caused subacute hepatic damage, featuring significantly less body weight gain and hepatic protein contents and higher liver weight, serum AST and ALT levels, and hepatic malondialdehyde and hydroxyproline contents with subacute hepatic damage-related histopathology of the liver. However, the CCl(4)-induced toxic effects were dramatically and dose-dependently inhibited by PR extract treatment. Thus oral administration of PR extracts significantly reduced CCl(4)-induced subacute hepatic damage in rats, probably by exerting a protective effect against hepatocellular necrosis via its free radical scavenging ability.     

The potential role of combined anti-oxidants against cadmium toxicity on liver of rats

Cadmium (Cd), a widely distributed toxic trace metal, has been shown to accumulate in liver after long- and short-term exposure. Cd (2 mg/kg/day CdCl2) was intraperitoneally given to rats for eight days. Vitamin C (250 mg/kg/day) + vitamin E (250 mg/kg/day) + sodium selenate (0.25 mg/kg/day) were given to rats by oral means. The animals were treated by anti-oxidants one hour prior to treatment with Cd every day. The degenerative changes were observed in the groups given only Cd and anti-oxidants + Cd. Metallothionein (MT) immunoreactivity increased in cytoplasm of hepatocytes of the rats given Cd when compared with controls. In a number of cells with Cd and anti-oxidants treatment, immunoreactivity increase was more than in the group given Cd only and nuclear MT expression was also detected. Cell proliferation was assessed with proliferating cell nuclear antigen (PCNA) immunohistochemistry. PCNA expressions increased in all groups more than in the controls. Anti-oxidants treatment increased cell proliferation. In the animals administered with Cd, an increase in serum aspartate (AST) and alanine (ALT) aminotransferases, liver glutathione (GSH) and lipid peroxidation (LPO) levels were observed. On the other hand, in the rats treated with anti-oxidants and Cd, serum AST and ALT, liver glutathione and LPO levels decreased. As a result, these results suggest that combined anti-oxidants treatment might be useful in protection of liver against Cd toxicity.     

A study on cadmium-induced nephropathy in rats pretreated with puromycin aminonucleoside

Nephrotoxicity of cadmium (Cd) was investigated using puromycin aminonucleoside (AN)-pretreated rats. AN pretreatment was performed by iv injection of 100 mg AN/kg body wt 11 days before the initial Cd injection. Since massive proteinuria and focal glomerular deposits were recognized, glomerular permeability is considered to be increased in AN-pretreated rats. AN-pretreated and intact rats were injected sc with 3 mg Cd/kg body wt, 4 times a week. In non-pretreated rats, slight tubular vacuolation was seen after 1-week Cd exposure and severe vacuolation and coagulative necrosis of the tubules was observed after 2-week Cd exposure. On the other hand, AN pretreatment delayed the onset of vacuolation and necrosis for 1 week and made the lesion milder. After 1-week Cd exposure, a larger amount of Cd was excreted into the urine of AN-pretreated rats than of non-pretreated ones, whereas Cd accumulation in the kidney and liver was lower in AN-pretreated rats than in non-pretreated ones. Thereafter, no difference in Cd concentration was recognized between two groups. From these findings, it is suggested that in early stage of Cd administration, Cd was filtered through the glomerular basement membrane modified by AN pretreatment and that this filterable Cd did not have nephrotoxic effects in AN-pretreated rats.     

异搏定和氯丙嗪对镉慢性肾毒性影响的实验研究

目的:对慢性镉染毒(Cd)大鼠投予异搏定(Ver)和氯丙嗪(CPZ),探讨这两种物质对镉慢性肾损伤的影响。方法:实验用4组大鼠,单纯镉染毒组和Ver、CPZ预处理组均皮下注射含Cd 1．4mg／kg的氯化镉(CdCl2)溶液,每周3次,连续6周。Ver和CPZ预处理组在每次皮下注射CdCl2前1h,分别向腹腔注射Ver 4mg／kg和CPZ 5mg／kg,,对照组大鼠在相同时间注射生理盐水5ml／kg,,在实验开始后第2,4,6周时收集尿样,测定尿N-乙酰-B—D-氨基葡萄糖苷酶(NAG)活力和尿蛋白含量。最后一次注射后24h处死大鼠,采集血液,取肾脏,测定血清尿素氮(BUN),血、肾皮质和尿中的Cd、Ca及血、肾皮质中丙二醛(MDA)含量。结果镉染毒4周时,与单纯镉染毒组比较,Ver和CPZ预处理组的尿NAG活力和尿蛋白含量均明显降低;镉染毒6周时,Ver和CPZ预处理组的血Cd、血清BUN、尿Ca及肾皮质MDA含量均明显降低。CPZ预处理组肾皮质Cd和血MDA含量也明显降低。结论:Ver和CPZ具有防止镉所致慢性肾损伤的作用,其机制可能是减轻镉对肾脏的脂质过氧化损伤。     

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.     

Mitochondrial effects of low-level cadmium in rats: Interaction with zinc

Male Sprague-Dawley rats were treated with sodium or cadmium (Cd) 4 acetate (25 g Cd per kg body weight) orally 5 times a week for 6 weeks. A second group of animals was repeatedly injected with zinc sulphate (6 and 12 mg zinc (Zn) per kg ip) with or without Cd gavage. Cadmium treatment alone yielded no obvious toxic effects as evidenced by serum constituents or animal weight gain. Similarly, Zn injection did not affect these criteria. Zinc injection increased metallothionein in liver and kidneys and increased renal Cd. Cytosolic sorbitol dehydrogenase was not influenced by either cadmium, Zn or Cd + Zn exposure. However, individual Cd gavage decreased mitchochondrial cytochrome c oxidase in liver by 50%. This was partly protected by Zn. Hepatic adenosine triphosphatase (ATPase) was not affected by any of the treatment regimens. However, renal ATPase was inhibited by combined Cd + Zn administration. The data suggest subcellular toxic effects due to treatment with low Cd doses as evidenced by the decrease in hepatic cytochrome c oxidase. Simultaneous Zn injection may reduce this effect of Cd in liver. However, the treatment of rats by low level Cd gavage combined with zinc administration impairs the animals' health as shown by weight loss.Abbreviations Cd cadmium - Zn zinc - ATP adenosine triphosphate - ATPase adenosine triphosphatase - MT metallo thionein - NADH nicotinamide adenine dinucleotide, reduced Parts of this study have been presented at the 20th Annual Meeting of the Australasian Society for Clinical and Experimental Pharmacologists (ASCEP), Dec 8–10, 1986, Melbourne.     

4种富硒植物预防MNNG诱发大鼠胃癌效果研究 二、不同源硒预防大鼠胃癌的安全性对比研究

目的对比研究长期摄入高剂量不同源硒的安全性。方法以亚硒酸钠为对照硒材料,采用N-甲基-N′-硝基-N-亚硝基胍(MNNG)诱发大鼠胃癌模型,连续灌以4种不同富硒植物(高剂量硒)17周,测定肝脏谷胱甘肽硫转移酶(GST)、血清谷草转氨酶(AST)和血清谷丙转氨酶(ALT)活性,并观察肝脏和肾脏的病理变化。结果各组大鼠肝GST活性均无显著性差异;75μg/kg bw(以Se计,下同)亚硒酸钠低剂量组大鼠血清AST和ALT活性不仅显著高于空白对照和MNNG组,而且显著高于150μg/kg bw和300μg/kg bw植物硒处理组(P<0.05)。病理分析发现75μg/kg bw亚硒酸钠低剂量组胆管周围有棕黄色颗粒,窦内枯否氏细胞轻度肥大、增生;其余各组未发现有意义的病变。结论亚硒酸钠毒性至少是实验用其它富硒植物的4倍。     

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.