Zhang Yan-shu, Yao Lin, Hao Yu-lan, Zou Yan, Xu Hou-jun, Fan Qi-yuan
Department of Preventive Medicine, North China Coal Medical University, Tangshan 063000, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2010 Mar;28(3):186-9.
To explore the biomarkers of manganese exposure by measuring the manganese (Mn) and iron (Fe) level as well as the mRNA change of Hepcidin, divalent metal-ion transporter-1 (DMT1) and Parkin-2, one of genes related to Parkinson disease in body fluid and brain tissues of rat.
Male Sprague-Dawley rats were administered (i.p) either MnCl2 solution (6 mg Mn/kg) or the same volume saline, 5 times per week and for 4 weeks. Graphic furnace Atom Absorption Spectrum (AAS) was applied to measure the concentration of Mn and Fe in brain tissue and body fluids. Meanwhile Hepcidin, DMT1 and Parkin-2 mRNA expression were detected by real-time RT-PCR.
Mn concentration in erythrocytes of rats was the 86.9 folds of that in control; No significant change was found in plasma. However the trend and range of Mn increase in cerebrospinal fluid (CSF) was the same as that in brain tissue including striatum, cortex, hippocampus and choroid plexus. Meanwhile Fe concentration in brain tissue of Mn exposed rats was also higher than that of control, whose trend was as same as that in CSF. However iron concentration in plasma decreased. The real-time RT-PCR data also showed that Hepcidin mRNA expression in Mn-exposed rat decreased 56% in blood, which was in line with its expression in cortex(67%). Similarly, Parkin-2 mRNA expression decreased both in blood (42%) and in striatum. However DMT1 mRNA expression increase 38% in striatum of Mn-exposed rats but decreased in blood.
Hepcidin and Parkin-2 mRNA expression in blood might be serves as the effective biomarkers following manganese exposure, certainly which needs to be further explored.
通过检测大鼠体液和脑组织中锰(Mn)、铁(Fe)水平以及与帕金森病相关基因之一的铁调素、二价金属离子转运体1(DMT1)和帕金2(Parkin-2)的mRNA变化,探索锰暴露的生物标志物。
雄性Sprague-Dawley大鼠腹腔注射MnCl2溶液(6 mg Mn/kg)或等体积生理盐水,每周5次,共4周。采用石墨炉原子吸收光谱法(AAS)测定脑组织和体液中Mn和Fe的浓度。同时,通过实时RT-PCR检测铁调素、DMT1和Parkin-2 mRNA的表达。
大鼠红细胞中Mn浓度是对照组的86.9倍;血浆中未发现明显变化。然而,脑脊液(CSF)中Mn增加的趋势和范围与包括纹状体、皮质、海马和脉络丛在内的脑组织相同。同时,锰暴露大鼠脑组织中的Fe浓度也高于对照组,其趋势与CSF中的相同。然而血浆中铁浓度降低。实时RT-PCR数据还显示,锰暴露大鼠血液中铁调素mRNA表达下降56%,这与其在皮质中的表达一致(67%)。同样,帕金2 mRNA在血液(42%)和纹状体中的表达均下降。然而,锰暴露大鼠纹状体中DMT1 mRNA表达增加38%,但在血液中下降。
血液中铁调素和帕金2 mRNA表达可能作为锰暴露后的有效生物标志物,当然这还需要进一步探索。