【作者】 李锋平；

【导师】 廖惠珍；

【作者基本信息】 福建医科大学 ， 卫生毒理学， 2005， 硕士

【摘要】 目的:低水平铅暴露带来的健康问题日趋突出,但其传统疗法会导致机体钙、锌等营养素流失和其它副作用。本课题研究维生素B₁ 的驱铅作用及对营养素钙、锌水平的影响,为长期低水平铅暴露人群的安全保健提供科学实验依据。方法:1、动物实验60 只清洁级雄性SD 大鼠按体重区组随机分为6 组:（I）阴性对照组、（II）VitB₁组、（III）单染铅组、（IV）铅+低剂量VitB₁组、（V）铅+中剂量VitB₁组、（Ⅵ）铅+高剂量VitB₁ 组。（I）和（II）组给予去离子水自由饮用,其余各组每天给予含铅量为400mg/L 的去离子水溶液自由饮用,每天记录各组大鼠的饮水量; 染毒的同时分别给予不同的干预因素:（I）与（III）组给予0.9%NaCl注射液腹腔注射;（II）、（IV）、（V）、（Ⅵ）组分别给予16.7mg/Kg、8.3mg/Kg 、16.7mg/Kg、33.4mg/Kg VitB₁腹腔注射,每日1 次,连续30 天;实验结束时收集相关标本进行铅、钙、锌含量的测定。2、细胞学实验（1） 维生素B₁对染铅红细胞的驱铅作用:实验设立11组。以健康人新鲜抗凝血为受试对象,在含铅量分别为0和5ug.ml^-1的体系孵化培养,不同浓度的维生素B1在不同的状态（①预防性驱铅:VitB₁先与细胞孵化后加铅;②治疗性驱铅:铅先与细胞孵化后加VitB₁;③无铅的状态）下干预相同的时间,实验重复2次,之后测定各组红细胞的铅含量。（2）维生素B₁对染铅红细胞内钙、锌的影响:实验分组及处理同方法（1）,实验结束后测定红细胞钙、锌含量。实验重复2次。更多还原

【Abstract】 Objective:The healthy problem brought by low-level lead exposure is gradually outstanding,but the tradional therapy often induce depletion of nutrition such as calcium 、zincand other by-effects. The topic was to study effect of vitamin B1 on lead excretion inlow-level lead and its influence on levels of calcium and zinc. This study was also toprovide the scientific evidences for the prevention and health-care of people exposingin low-level lead environment.Methodes:1、Animal experiment70 male Sprague-Dawley rats were weighted and assigned randomly to sevengroups based on body-weigh including:（I）control, （II）VitB₁, （III）Pb,（IV）Pb + low-dose VitB₁, （V）Pb +middle-dose VitB₁, （Ⅵ）Pb +high-dose VitB₁ . Therats in control and VitB₁ groups ate and drank deionized water freely, the other fivegroups drank 400mg/L lead acetate （mixed by deionized water） freely. The amountsdrunk by each group were noted in order to account the total amounts of lead. Meanswhile,（I）and（III）groups were administered （daily intraperitoneal （i.p.） injection ,perday i.p.） in saline, while（II）、（IV）、（V）、（Ⅵ）groups in VitB₁ （ 16.7mg/Kg、8.3mg/Kg 、16.7mg/Kg、33.4mg/Kg body weight per day i.p. respectively） during for30 days . After the experiment, the rats were sacrificed and samples such as serum,urine, feces, liver and femor were taken for test.2、Cell Assays（1） Study effect of vitamin B₁ on lead excretion in red cell: The assay include elevengroups. Fresh red cells from health people were incubated in two differentconcentrations of lead （0,5ug.ml-1） and treated with various concentrations of vitaminB1 （0, 250ug/6ml, 500ug/6ml, 1000ug/6ml）at the different states （that is , ①Preventive lead toxicity: red cell were pre-incubated with the VitB1 then with the lead②Treatment lead toxicity: red cell were pre-incubated with the lead then with theVitB1 ③red cell were incubated only with the VitB1） and incubated in the sametime（the experiment was repeated 2 times）. After incubation, the content of cell leadwere measured.（2） Exploring the influence of calcium and zinc while vitamin B1 affect lead excretionin red cell : According to the methods of （1）, contents of cell calcium and cell zinc weremeasured（the experiment was repeated 2 times）.Results:1、Explore effect of vitamin B1 on lead excretion and its influence on Calcium andZinc:（1） VitB1 can accelerate the excretion of lead. Results from animal experimentdemonstrated that blood lead、liver lead、femor lead、urine lead and feces leadconcentrations of Pb group increased more significantly than that of controlgroup（P<0.05）. But after intervened by VitB1,a significant reduction of blood lead andliver lead concentrations and an evident increasing of urine lead in group（IV）、（V）、（Ⅵ）were observed（P<0.05）; We also found that the concentrations of lead and VitB1had obvious dose-effect relationship（P<0.05）. The results also indicated low-doseVitB1 could reduce significantly the concentration of lead in femor. Same results fromcell assay showed that , the concentration of lead in red cell incubated in Pb increasedsignificantly（P<0.05）. When cells were treated with different content of VitB1 atdifferent states , lead concentrations of preventive groups or treatment groups were allreduced significantly（P<0.05）. The obvious dose-effect relationships between theconcentration of lead and VitB1 were found.（2）VitB1influencing on calcium and zinc①VitB1influenced on calcium while it affected on lead: Assays showed that rats in Pbgroup excreted more urine calcium significantly than in control group（P<0.05）, and asignificant reduction of urine calcium in middle and high-dose VitB1 given werefound（P<0.05）. Cell assays revealed VitB1 had singnificantly effects on theconcentrations of cell calcium while cell was treated with combination Pb, theconcentrations of cell calcium increased significantly（P<0.05） and existed an obviouspostive relationship between VitB1 and Pb（r=0.605,P=0.000）.②VitB1influence on zinc content while it affect on lead: Assays showed that rats inPb group excrete more urine zinc significantly than in control group, and a significantreduction of urine zinc in middle and high-dose VitB1 given were found（P<0.05）. Cellassays revealed cell zinc treated with lead alone existed the trend of reduction, butafter prevention or treatment, the zinc contents gained partial recovery but weren’tsignificant（P>0.05）.2、Explore partial possible mechanisms of excreating Pb intervened by VitB1 :①Results from cell assays showed cell lead concentrations in three doses ofpreventive groups and three doses of treatment groups were obvious lower than in Pbgroup（P<0.05）. So we concluded that VitB1 could reduce the cell lead concentrationthrough accelerating to excrete Pb from cell or prohibiting Pb entering to cell.②Animal experiment results revealed that the excretions of urine calcium werereduced significantly. And cell assay results that cell calcium was increasedremarkably（P<0.05）. So we concluded that cell lead concentration would be reducedby Ca2+regulated by VitB1.③Animal experiment results urine zinc concentrations increased significantly in ratstreated with Pb merely（P<0.05）. But the urine zinc concentrations were reverse whenrats treated with combination VitB1 and Pb （P<0.05）. So we concluded that leadconcentration would be reduced by zinc regulated by VitB1.Conclusion:1、VitB1 can accelerate accumulative lead to excrete, and the concentration betweenVitB1 and lead existed dose-effect relationship.2、VitB1 can reduce the excretion of calcium in rats exposed in low-level lead andraise the contents of calcium of cell incubated in lead..3、VitB1 can reduce the excretion of zinc in rats exposed in low-level lead and existthe trend of raising the zinc content of cell incubated in lead .4、VitB1 accelerating lead to excrete maybe exist partial mechanisms as follows:1)Accelerating to excrete Pb from cell or prohibiting Pb entering to cell aremechanisms of VitB1 against accumulative lead.2) VitB1 regulating calcium and zinc concentration to accelerate lead to excrete maybeits another mechanisms.更多还原