外周血单个核细胞线粒体功能失调作为锰神经毒性早期效应标志的人群研究

Mitochondrial dysfunction in peripheral blood mononuclear cells as an effect biomarker of neurotoxicity induced by manganese

目的探讨以外周血单个核细胞线粒体功能失调作为锰神经毒性早期效应标志的可能性。方法选取已脱离锰接触的锰中毒病人18名作为中毒脱离接触组,选取锰作业工人73名作为锰接触组,选取无职业性锰接触人群63名作为对照组,对锰作业现场进行劳动卫生学监测,对中毒脱离接触组、接触组及对照组人群进行一般健康状况及神经系统检查,并对接触组和对照组进行神经行为功能核心组合测试(NCBT),检测3组人群外周血单个核细胞线粒体功能(呼吸控制率、ATP生成、线粒体膜电位),并对接触组神经行为指标与线粒体功能失调进行相关性分析。结果锰作业现场中拌粉机旁及其二层投料口粉尘浓度严重超标,高达16.3和38.0 mg/m3,分别超标1.63和3.8倍(卫生标准为10 mg/m3,TJ36-79),其中MnO2浓度为0.84和1.51 mg/m3,超标4.2和7.6倍(卫生标准为0.2 mg/m3,TJ36-79);一般健康状况及神经检查发现,中毒脱离接触组和接触组均有头晕、头痛、记忆力减退、注意力分散等植物神经紊乱等症状,中毒脱离接触组中有震颤及共济运动失调等锥体外系损害体征,接触组未见锥体外系神经系统损害体征;接触组与对照组NCBT神经行为功能检测发现,接触组易出现疲倦感,简单反应时较对照组显著增加,数字跨度、视觉记忆和目标追踪试验与对照组比较,差异有统计学意义;接触组血单个核细胞线粒体功能指标RCR、ATP生成及线粒体膜电位较对照组均显著降低,差异均有统计学意义(P<0.05),而中毒脱离接触组与对照组比较,差异无统计学意义(P>0.05);相关分析表明,接触组简单反应时、数字跨度与线粒体功能指标改变具有相关性(P<0.05或P<0.01)。结论锰接触可导致外周血单个核细胞线粒体功能失调,对于锰接触者外周血单个核细胞线粒体功能失调可作为潜在的锰神经毒性早期效应生物标志。

Objective To study the possibility of mitochondrial dysfunction in peripheral blood mononuclear cells as a potential early effect biomarker of manganese neurotoxicity. Methods Eighteen manganism patients who have been out of manganese exposure were selected as poisoned group isolated exposed,73 workers occupationally exposed to manganese as exposure group and 63 workers without manganese exposure as control group. The labor hygiene surveying,neurological examination for the poisoned group isolated exposed,exposure group and control group,neurobehavioral test battery（ NCTB） for the exposure group and control group were performed. The mitochondrial functions（ respiratory control ratio,ATP production,mitochondrial membrane potential） in peripheral blood mononuclear cells were examined. Results The concentration of manganese dust and manganese in the workshop air exceeded the national hygiene standards.The signs and symptoms such as tremor and ataxia of extrapyramidal damage in manganism group,behavioral dysfunction of learning,memory and reduced respond ability in the exposure group were observed. Compared with the control group,in the exposure group respiratory control ratio,ATP generation and mitochondrial membrane potential significantly decreased（ P〈0. 05）. The correlation analysis showed that simple reaction time,digit span and indicators of mitochondrial dysfunction have significant correlation（ P〈0. 05 or P〈0. 01） in the exposure group. The mitochondrial function in peripheral blood mononuclear cells in manganism group was not significantly different（ P〉0. 05）compared with the control group. Conclusion The manganese exposure can result in mitochondrial dysfunction in peripheral blood mononuclear cells. The mitochondrial dysfunction in peripheral blood mononuclear cells can be used as a potential early biomarker of neurotoxic effects induced by manganese.