新型络合剂对大鼠肾镉促排作用初探

新型络合剂对大鼠肾镉促排作用初探马东星赵金垣王超马佩云刘宏张亨山二硫代氨基甲酸酯类（ＤＴＣ）络合剂对体内蓄积镉的促排作用，是当前镉中毒促排治疗的热点［１～３］。本次实验观察了最新设计合成的７种ＤＴＣ类络合剂对染毒大鼠肾内镉的促排作用，并与美国新近研制...     

新型络合剂MeOBGDTC对尿镉及微量元素排泄的影响

以依地酸二钠钙（Ｃａ—ＥＤＴＡ）为对照，观察了４—甲氧苄基Ｄ—葡糖胺—Ｎ—二硫代羧酸钠（ＭｅＯＢＧＤＴＣ）对染镉大鼠尿镉及尿锌、铜、铁、锰等微量元素的促排作用。给大鼠腹腔注射４．４４８μｍｏｌＣｄ（２＋）ｋｇ（－１）日（－１）的氯化镉，共４周。然后分别投以８８９．６００μｍｏｌｋｇ（－１）日（－１）的Ｃａ—ＥＤＴＡ和ＭｅＯＢＧＤＴＣ，共５次。结果表明：Ｃａ—ＥＤＴＡ和ＭｅＯＢＧＤＴＣ均能显著增加大鼠的尿镉水平，并可持续至第５给药日，分别达单纯染镉组的１．４６～３．４５倍和１．４０～３．３３倍；Ｃａ－ＥＤＴＡ还能明显增加大鼠尿锌、锰及铁的排泄，而ＭｅＯＢＧＤＴＣ对此则无明显影响。     

乙醇对雄性生殖内分泌系统的损害及其机制

目的研究乙醇对雄性生殖内分泌系统损害机制。方法测定饮酒和酒精中毒者血Ｔ、ＬＨ、ＦＳＨ、Ｅ２、ＬＤＨ、ＬＤＨ－Ｘ、Ｇ－６ＰＤ水平和乙醇染毒大鼠血和睾丸匀浆Ｔ、ＬＨ、ＦＳＨ、ＭＤＡ、ＳＯＤ、ＧＳＨ－ＰＸ、ＣＡＴ、－ＳＨ水平。结果３０００、４０００ｍｇ／ｋｇ染毒７０天大鼠血Ｔ明显下降,ＬＨ、Ｅ２、ＦＳＨ升高,血和睾丸匀浆ＭＤＡ明显升高,而ＳＯＤ、ＧＳＨ－ＰＸ－ＳＨ明显下降,饮酒和酒精中毒者血Ｔ明显下降,     

应用单细胞凝胶电泳技术检测辐射致外周血淋巴细胞DNA损伤

应用单细胞凝胶电泳试验 （ＳＣＧＥ） 分别检测了受γ射线照射后小鼠及从事Ｘ 射线探伤工人的外周血淋巴细胞ＤＮＡ 单链断裂（ｓｓｂ） , 结果发现： ０－５Ｇｙ 和５－０Ｇｙ 的γ射线照射组小鼠, 外周血淋巴细胞彗星百分率显著高于对照组; 从事Ｘ 射线探伤工人的外周血淋巴细胞彗星百分率也显著升高。提示ＳＣＧＥ 检测的ＤＮＡｓｓｂ 可作为射线对健康影响的早期生物学指标。     

二硫化碳对大鼠肝脏脂质过氧化作用的研究

观察了二硫化碳（ＣＳ２）腹腔注射染毒对大鼠肝脏脂质过氧化物（ＬＰＯ）含量超氧化物歧化酶（ＳＯＤ）和谷胱甘肽过氧化物酶（ＧＳＨ－ＰＸ）活力的影响，急性染毒实验结果显示，大鼠肝ＬＰＯ含量随ＣＳ２染毒剂量增加而明显升高（ｒ＝０．８１０８，Ｐ＜０．０１），ＳＯＤ活性随剂量增加有降低趋势，ＧＳＨ－ＰＸ活性未见显著变化。亚急性实验结果显示，染毒２１ｄ染毒组ＧＳＨ－ＰＸ活力，染毒４５ｄ染毒组ＳＯＤ及ＧＳＨ－ＰＸ活力与对照组比较均显著降低（Ｐ＜０．０５），这表明，ＣＳ２是一个重要的致脂质过氧化物。     

急性染镉对小鼠肝肝肾组织谷胱甘肽的影响

目的 探讨氯化镉急性染毒对小鼠肝脏、肾脏胱甘肽（ＧＳＨ）代谢的影响。方法 给小鼠一次性腹腔注射不同剂量氯化镉,９小时后测定肝,肾组织镉、丙二醛（ＭＤＡ）、ＧＳＨ含量。结果 各剂量组肝、肾镉含量升高,高剂量组肝、肾ＭＤＡ含量升高,肾ＧＳＨ含量下降,肝脏ＧＳＨ呈现先升高,后下降的剂量反应关系,。结论氯化镉染毒９小时后可同时在小鼠肝、肾脏蓄积、并引起肝肾脂质过氧化反应,小鼠肝、肾脏对急性镉染毒诱导的ＧＳ     

BSO和NAC对镉急性毒性影响的实验研究

给仓鼠皮下注射不同剂量氯化镉后２４小时,测定血清ＬＤＨ、ＧＰＴ,尿ＬＤＨ和蛋白质,肝脏和肾皮质镉和ＧＳＨ含量。结果发现高剂量染镉后血清ＬＤＨ和ＧＰＴ活性,肝肾镉含量和肾皮质ＧＳＨ含量增高。表明急性染镉可引起仓鼠肝脏损害。给仓鼠ＢＳＯ或ＮＡＣ预处理后再投与镉,发现ＢＳＯ可增加镉的肝肾毒性,而ＮＡＣ能拮抗镉的肝毒性,增加镉的肾毒性。推测其机理与ＢＳＯ或ＮＡＣ预处理后使机体细胞内ＧＳＨ含量改变有关。     

不同镉锌比例的镉－金属硫蛋白致肾损害的实验研究

本文通过皮下注射不同镉锌比例的Ｃｄ－ＭＴ，来观察大鼠肾功能变化，结果显示：进入大鼠体内的镉主要在肾脏中蓄积，且随注射Ｃｄ－ＭＴ中镉的比例增高而增高；试验组肝、肾中锌的含量高于对照组，其中与Ｃｄ－ＭＴ中镉的比例有一定的关系；注射含镉比较高的大鼠其尿酶（ＮＡＧ、γ－ＧＴ）和尿蛋白（总蛋白和白蛋白）均显著高于对照组。提示：进入生物体内的镉主要以Ｃｄ－ＭＴ形式运输到肾脏；镉可影响生物体内锌的分布，且锌对镉的毒作用有一定的拮抗作用；镉性损伤以肾小管为主，一定程度可累及肾小球。     

锌,硒对镉损伤肾脏的保护作用的探讨

使用考马斯亮蓝法、碱性苦味酸法、黄嘌呤氧化酶法分别测定镉组、镉锌组、镉硒组及对照组大鼠尿蛋白、尿肌酐、肾组织总超氧化物歧化酶（Ｔ－ＳＯＤ）活力。结果表明，染毒３周后，镉组大鼠尿蛋白、尿肌酐显著增高，肾组织Ｔ－ＳＯＤ活力受到抑制，且均与对照组有显著性差异（Ｐ＜０．０５），而镉锌组、镉硒组各指标均与对照组无显著性差异（Ｐ＞０．０５），且镉硒组各指标较镉锌组更接近于对照组。证实了镉的肾毒性作用及锌、硒的拮抗作用，并初步显示锌的作用较硒为弱。     

镉对肾脏的毒作用

雄性Ｗｉｓｔａｒ大鼠２４只，随机等分为４组，皮下注射不同剂量的ＣｄＭＴ。结果显示镉接触组尿钙和尿蛋白都高于对照组；肾皮质钠泵和钙泵活性低于对照组，体外试验也显示镉能抑制钙泵活性，ＧＳＨ和半胱氨酸对这种抑制有保护作用；肾皮质ＧＳＨ含量低于对照组，ＭＤＡ含量则高于对照组，但肝脏的这两个指标无变化；高剂量组ｃＡＭＰ／ｃＧＭＰ的比值低于对照组。提示脂质过氧化和钙代谢障碍是镉引起肾损害的机理之一。     

Effects of dietary zinc and cadmium on tissue selenium concentration and glutathione peroxidase activity in rats fed DL-selenomethionine or sodium selenite.

The effects of dietary zinc (Zn) and cadmium (Cd) on tissue selenium (Se) concentration and glutathione peroxidase (GSH-Px) activity were studied in weanling male Wistar rats. One group of rats was fed a purified diet based on casein and sucrose, and the other rats used in a 2 x 2 x 2 factorial arrangement of treatment were fed this diet supplemented with 0.1 mg Se/kg, either as DL-selenomethionine or sodium selenite and plus 100 mg Zn/kg as zinc sulfate or 5 mg Cd/kg as cadmium chloride or both for 4 weeks. Se concentrations in plasma, erythrocytes, muscle, heart, and liver were significantly elevated by Zn. Cd significantly decreased Se concentration in muscle. Addition of Zn to the diets markedly increased (p less than 0.001) hepatic GSH-Px activity. However, Cd in the diets produced a significant increase (p less than 0.001) in erythrocyte GSH-Px activity. These results indicate that Zn level of marginal deficiency (8.6 mg/kg diet) can decrease Se availability and a small excess of Zn increases Se availability for hepatic GSH-Px activity.     

硒镉摄入对大鼠脏器中硒、镉、铜、锌、锰含量的影响

目的：探讨硒镉摄入对大鼠脏器中硒、镉、铜、锌、锰含量的影响。方法：用含5ppm硒、50ppm镉和含5ppm硒＋50ppm镉的水,供3月龄的Wistar雄性大鼠自由饮用,3周后用原子吸收分光光度法测定大鼠肝、肾、脾和睾丸中硒、镉、铜、锌和锰的含量。结果：5ppm硒组大鼠4种组织中硒、铅含量、肝脾组织中锌含量和肾、脾、睾丸组织中铜含量均高于对照组;50ppm镉组大鼠4种组织中镉的含量、肾脾组织中硒的含量和肝脾组织中铜锌含量均高于对照组;经口同时摄入硒、镉时大鼠4种脏器组织中硒的含量明显低于硒组,4种脏器组织中镉的含量明显高于硒组,肝脏组织中锌的含量显著低于镉组,脾脏组织中锌的含量显著低于硒组,肾、脾、睾丸组织中铜的含量低于硒组,肾、睾丸组织中锰的含量低于镉组。     

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.     

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。     

亚硒酸钠对镉和汞肝肾氧化损伤影响的实验研究

目的:观察一次染镉和汞对大鼠肝、肾组织氧化损伤作用,探讨亚硒酸钠预处理对镉和汞氧化损伤的影响。方法:Wister大鼠48只,随机分成6组,每组8只,第1组为染镉实验对照组,第2组为单纯染镉组,第3组为亚硒酸钠预处理组,第4组为染汞实验对照组,第5组为单纯染汞组,第6组为亚硒酸钠预处理干预组。第1、4组大鼠先腹腔注射生理盐水,2 h后皮下注射生理盐水。第2组大鼠先腹腔注射生理盐水,2 h后皮下注射35μmol/kg氯化镉溶液。第3组大鼠先腹腔注射10μmol/kg亚硒酸钠溶液,2 h后皮下注射35μmol/kg氯化镉溶液。第5组大鼠先腹腔注射生理盐水,2 h后皮下注射2.5 mg/kg HgCl2溶液,第6组大鼠先腹腔注射20μmol/kg亚硒酸钠溶液,2 h后皮下注射2.5 mg/kg HgCl2溶液。染毒24 h后测定肝、肾皮质镉或汞、谷胱甘肽、丙二醛含量和谷胱甘肽过氧化物酶活性。结果:与对照组比较,单纯染镉组大鼠肝GSH、MDA含量显著升高,GSH—Px活性显著下降。Na2SeO3预处理组肝、肾皮质GSH和镉含量显著降低,肝脏GSH—Px活性及肾皮质MDA含量显著升高。单纯染汞组大鼠肝、肾皮质及尿汞含量均显著高于对照组。单纯染汞组肝MDA含量显著高于对照组,GSH含量和GSH—Px活性显著低于对照组。Na2SeO3预处理组的肝脏GSH含量和GSH—Px活性均较单纯染汞组升高,有显著性差异。单纯染汞组肾皮质MDA含量显著高于对照组,GSH含量和GSH—Px活性显著降低。Na2SeO3预处理组中肾皮质MDA含量低于单纯染汞组,GSH—Px含量高于单纯染汞组。结论:给大鼠一次染镉和汞,可以对肝和肾脏产生明显的氧化损伤作用。亚硒酸钠对急性染镉和汞所致肝肾损伤具有一定的拮抗作用,其机制可能与增加内源性GSH、使GSH—Px活性增强以及清除自由基能力提高有关。     

Correlation of cadmium-induced nephropathy and the metabolism of endogenous copper and zinc in rats

Female Wistar rats were injected (sc) every second day for 8 weeks with Cd (0.25 mg/kg) as CdCl2. After only a 2-week exposure, when cadmium (Cd) concentration in liver was about 13 micrograms/g, ultrastructural examinations revealed some irregular ergastoplasm systems and significant proliferation of smooth endoplasmic reticulum in the hepatocyte ultrastructure. The increase in Zn content occurred simultaneously with the increase in Cd concentration in the liver (Zn to Cd ratio was 1:1). In the kidneys after a 3-week exposure, when Cd concentration was 7 micrograms/g, the concentration of endogenous Cu increased. At the same time the urinary excretion of that metal was considerably higher than that of the control group. In the kidneys after a 4-week exposure, when Cd concentration in this organ exceeded 10 micrograms/g tissue, injured brush border microvilli and swollen mitochondria in the proximal convoluted tubular cells were seen. In renal corpuscules, fusion between the podocyte pedicles was also found. The changes in renal cortex ultrastructure became more pronounced when Cd concentration in kidney was increasing. Necrotic changes in the examined organ were observed when Cd concentration increased to about 30 micrograms/g tissue. The critical concentration in renal cortex of about 200 micrograms/g tissue should be revised. The present margin of safety with regard to risk of renal effects is small.     

Analysis of the renal tissue of a woman chronically exposed to cadmium

Summary In a 61-year-old woman, who had been exposed for 20 years to cadmium in the production of Ni-Cd batteries, nephrectomy of the contracted kidney was performed. The removed kidney was examined histologically and the cadmium concentration was determined in the cortex (44.97 g g^–1) and in the medulla (7.71 g g^–1). The homogenates of the renal cortex and medulla were subjected to gel filtration on Sephadex G-75. In the cortex, as well as the medulla, cadmium was predominantly found in the low-molecular (metallothionein) fraction, but in the cortex, Cd content in this fraction was six times higher than in the medulla. The determination of SH groups and proteins in high- and low-molecular fractions indicates an induction of the metallothionein formation primarily in the renal cortex.     

Cadmium/zinc relationships in kidney cortex and metallothionein of horse and red deer: histopathological observations on horse kidneys

Cadmium and zinc were determined in kidney cortex of 63 horses and 51 red deer (Cervus elaphus). Cadmium and zinc were also determined in protein fractions obtained by Sephadex chromatography of kidney cortex from 10 horses and 4 red deer. Histopathological parameters in kidney cortex of horses were compared to cadmium content. The metal contents (on wet weight basis) in kidney cortex of the horses were 0.31 +/- 0.22 mmole Cd/kg (range 0.03-1.21) and 0.63 +/- 0.17 mmole Zn/kg (range 0.36-1.23). The Zn content increased with the Cd content, the Zn increase being less at higher concentrations. No significant increase of the Cd content with age of the horses (range 2-19 years) was found. The metal contents in kidney cortex of the red deer were 0.030 +/- 0.031 mmole Cd/kg (range 0.002-0.13) and 0.51 +/- 0.37 mmole Zn/kg (range 0.30-2.82). Here the Zn content did not increase significantly with Cd content, and in this case a positive linear relation of Cd content with age of the deer (range 0-11 years) was observed. The molar Zn/Cd ratio in the metallothionein fractions of horse kidney cortex was less variable at higher Cd contents. All Cd and the increase of Zn above an average basal level of 0.36 mmole Zn/kg was recovered in the metallothionein fractions. No gross histopathological changes could be observed in kidney cortex of the horses. Nevertheless a slight increase of the thickness of the basement membrane of Bowman's Capsule and also of the diameter of Bowman's Capsule in relation to Cd content up to 0.3 mmole/kg could be observed.     

镉,铂在体内的分布及其肝,肾损害的实验研究

研究了大鼠腹腔注射１．０ｍｇＣｄ２＋／ｋｇ体重的氯化镉和０．３２ｍｇＰｔ２＋／ｋｇ体重顺铂后，镉和铂在体内的分布及其肝、肾毒性。结果发现：镉主要分布于肝脏，随着染毒时间的延长，镉有向肾脏集中的趋势；铂主要分布于肾；氯化镉引起的肝损害发生在肾损害之前，氯化镉引起的肾损害与肝损害有关；顺铂引起的肝损害发生在肾损害之后，其肾损害与肝损害的发生无关。