【Objective】 Explore the effects of lead on hippocampus in central nervous tissue of developing rat. 【Methods】 A total of 48 rats(30-day old) were randomly divided into 4 groups for intragastrical perfusion of lead acetate[Pb(Ac)2]: untreated, low[2 mg/(kg·d)], medium[20 mg/(kg·d)], and high(200 mg/kg/d) dose groups. The rats were killed six weeks post perfusion. Pb content was determined in blood by using the graphite furnace atomic absorption spectrometry. The DMT1 gene expression was analyzed in the hippocampus by RT-PCR and western blot. 【Results】 The blood lead levels in lead treatment groups were significantly higher than that of the control group(P<0.01), indicating our lead poisoning rat model was successful. No significant difference of DMT1mRNA expression; however, DMT1 protein expression increased in low dose group. In medium and high dose groups, the increase of DMT1 expression were detected in both mRNA and protein level(P<0.05 or <0.01). Our data also displayed the linear correlation between blood lead level and the expression of DMT1 gene. 【Conclusions】 The neurotoxicity induced by high blood lead level was partly mediated by over-expression of DMT1 gene in the hippocampus of central nervous system.
Key words
lead /
hippocampus /
DMT1 /
neurotoxicity
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References
[1] Lidsky TI, Schneider JS. Lead neurotoxicity in children: basic mechanisms and clinical correlates[J]. Brain,2003,126(Pt1):5-19.
[2] Bellinger DC. Lead[J]. Pediatrics,2004,113(4):1016-1022.
[3] Bannon DI, Abounader R, Lees PS, et al. Effect of DMT1 knockdown on iron, cadmium, and lead uptake in Caco-2 cells[J]. Am J Physiol Cell Physiol,2003,284(1):C44-50.
[4] Liu J, Han D, Li Y, et al. Lead affects apoptosis and related gene XIAP and Smac expression in the hippocampus of developing rats[J]. Neurochem Res,2010,35(3):473-479.
[5] 王学谦,尹先仁,白雪涛.铅镉联合作用对大鼠肾小管上皮细胞脂质过氧化的影响[J].卫生研究,2002,4(31):232-234.
[6] Shi LZ, Zheng W. Early lead exposure increases the leakage of the blood-cerebrospinal fluid barrier, in vitro[J]. Hum Exp Toxicol,2007,26(3):159-167.
[7] Bradbury MW, Deane R. Permeability of the blood-brain barrier to lead[J]. Neurotoxicology,1993,14(2-3):131-136.
[8] 李国君,吴德生,肖邦良,等.铅对大鼠不同脑区IEG表达的影响[J].卫生研究,1999,2(28):65-69.
[9] Bannon DI, Portnoy ME, Olivi L, et al. Uptake of lead and iron by divalent metal transporter 1 in yeast and mammalian cells[J]. Biochem Biophys Res Commun,2002,295(4):978-984.
[10] Park JD, Cherrington NJ, Klaassen CD. Intestinal absorption of cadmium is associated with divalent metal transporter 1 in rats[J]. Toxicol Sci,2002,68(2):288-294.
[11] Trinder D, Oates PS, Thomas C, et al. Localisation of divalent metal transporter 1(DMT1) to the microvillus membrane of rat duodenal enterocytes in iron deficiency, but to hepatocytes in iron overload[J]. Gut,2000,46(2):270-276.
[12] Wardrop SL, Richardson DR. The effect of intracellular iron concentration and nitrogen monoxide on Nramp2 expression and non-transferrin-bound iron uptake[J]. Eur J Biochem,1999,263(1):41-49.
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