王馨, 张红梅, 宋展飞, 李阳阳, 苗慧德, 赵亭怡, 张志艳. 血浆脑源性神经营养因子水平在多环芳烃职业暴露与焦炉工人认知功能障碍关联中的中介效应[J]. 环境与职业医学, 2022, 39(3): 315-322. DOI: 10.11836/JEOM21370
引用本文: 王馨, 张红梅, 宋展飞, 李阳阳, 苗慧德, 赵亭怡, 张志艳. 血浆脑源性神经营养因子水平在多环芳烃职业暴露与焦炉工人认知功能障碍关联中的中介效应[J]. 环境与职业医学, 2022, 39(3): 315-322. DOI: 10.11836/JEOM21370
WANG Xin, ZHANG Hongmei, SONG Zhanfei, LI Yangyang, MIAO Huide, ZHAO Tingyi, ZHANG Zhiyan. Mediating effect of serum BDNF level on association of occupational PAHs exposure with cognitive impairment in coke oven workers[J]. Journal of Environmental and Occupational Medicine, 2022, 39(3): 315-322. DOI: 10.11836/JEOM21370
Citation: WANG Xin, ZHANG Hongmei, SONG Zhanfei, LI Yangyang, MIAO Huide, ZHAO Tingyi, ZHANG Zhiyan. Mediating effect of serum BDNF level on association of occupational PAHs exposure with cognitive impairment in coke oven workers[J]. Journal of Environmental and Occupational Medicine, 2022, 39(3): 315-322. DOI: 10.11836/JEOM21370

血浆脑源性神经营养因子水平在多环芳烃职业暴露与焦炉工人认知功能障碍关联中的中介效应

Mediating effect of serum BDNF level on association of occupational PAHs exposure with cognitive impairment in coke oven workers

  • 摘要: 背景 长期多环芳烃(PAHs)职业暴露是人群认知功能障碍发生的重要危险因素,同时还会引起脑源性神经营养因子(BDNF)降低,但BDNF在职业多环芳烃暴露致工人认知障碍中是否发挥关键作用尚未明确。

    目的 分析焦炉工外周血浆中PAHs水平与认知功能障碍的关联性,以及血浆BDNF水平在PAHs与认知功能障碍关联中的中介效应。

    方法 采用横断面调查研究,在太原市某大型企业抽取焦化厂(暴露组)和能源动力厂(对照组)工人,按年龄、教育程度、吸烟情况以1:1匹配获得138对工人为研究对象。通过问卷调查收集工人的基本资料,采用蒙特利尔认知评估(MoCA)量表评估工人的认知功能,收集空腹肘静脉血,用高效气相色谱-质谱串联法(GC-MS)检测血浆中16种PAHs的浓度,用酶联免疫吸附法(ELISA)测定血浆BDNF水平。采用多重线性回归模型分析血浆中12种PAHs水平与MoCA得分之间的关系,采用Bootstrap法对BDNF水平在二者关联中的中介效应进行分析。

    结果 工人年龄和工龄的均数±标准差分别为(48.46±5.05)岁和(21.45±9.78)年,以中专或高中及以上文化程度为主(58.7%)。暴露组血浆中Σ12PAHs水平的中位数及第25、75百分位数MP25P75)为20.937(9.454,38.387) μg·L−1,高于对照组水平9.997(4.952,23.770) μg·L−1;MoCA总分为(22.82±2.38)分,低于对照组(24.60±5.67)分(均P<0.05)。暴露组血浆BDNF水平为(29.99±9.80)μg·L−1,与对照组的水平(31.48±9.09)μg·L−1相比差异无统计学意义(P>0.05)。以工人血浆中PAHs为自变量,以MoCA总分为应变量,调整协变量后,多重线性回归模型分析结果表明,血浆中Σ12PAHs每增加1 μg·L−1,MoCA得分变化及其95%CI为−0.020(−0.035 ~ −0.005)分。按照工人血浆中Σ12PAHs水平的三分位数(8.31,23.76)μg·L−1为界,设置低(<P33)、中(P33~P66)、高(>P66)浓度3 组哑变量。与低浓度组相比,高浓度组MoCA得分下降1.167分,其95%CI为−1.866 ~ −0.467 分。血浆BDNF水平每增加1 μg·L−1,MoCA得分增加0.066分,其95%CI为0.012 ~ 0.119分。二分类logistic回归分析显示,Σ12PAHs高浓度组出现轻度认知功能障碍(MCI)的风险及其95%CI是低浓度组的2.635(1.085 ~ 6.398)倍。中介效应分析显示,血浆BDNF水平是PAHs与认知功能障碍之间的中间变量,在PAHs致认知功能障碍风险中,45.50%是由BDNF水平降低介导的。

    结论 焦炉工血浆PAHs水平与MoCA得分呈负相关,且PAHs可能通过降低血浆BDNF水平介导认知功能障碍。

     

    Abstract: Background Long-term occupational polycyclic aromatic hydrocarbons (PAHs) exposure is an important risk factor for cognitive impairment. At the same time, it can also cause a decrease of brain-derived neurotrophic factor (BDNF). However, it is not clear whether BDNF plays a key role in the cognitive impairment of workers caused by occupational PAHs exposure.

    Objective To analyze the correlation between the levels of PAHs in the plasma of coke oven workers and cognitive impairment, and to explore the possible mediating effect of plasma BDNF level on the relationship between PAHs and cognitive impairment.

    Methods A cross-sectional survey was carried out to select 138 pairs of workers from a coking plant (exposure group) and an energy plant (control group) in a large enterprise in Taiyuan, and the matching variables included age, education level and smoking status. The basic data of the workers were collected by questionnaire. The cognitive function of the workers was assessed by the Montreal Cognitive Assessment (MoCA) scale. Fasting elbow venous blood was collected, the plasma concentrations of 16 PAHs were determined by high performance gas chromatography-mass spectrometry (GC-MS), and the plasma concentration of BDNF was detected by enzyme-linked immunosorbent assay (ELISA). Multiple linear regression model was used to analyze the relationship between 12 PAHs levels in plasma and MoCA scores, and Bootstrap method was used to analyze the mediating effect of BDNF in the relationship between these two indicators.

    Results The average ( \bar x \pm s ) age of workers in the two groups was (48.46±5.04) years, the length of service was (21.45±9.78) years, and 58.7% of the participants reported their education level at secondary vocational school, high school, and above. The median level (25th and 75th percentiles) M(P25, P75) of plasma Σ12PAHs concentration of workers in the exposure group 20.937 (9.454, 38.387) μg·L−1 was significantly higher than that of the control group 9.997 (4.952, 23.770)μg·L−1 and the MoCA score (22.82±2.38) of the exposure group was significantly lower than that of the control group (24.60±5.67) (P<0.05). The plasma BDNF showed no significant difference between the exposure group (29.99±9.80) μg·L−1 and the control group (31.48±9.09) μg·L−1(P>0.05). Taking plasma PAHs as independent variable and MoCA score as dependent variable, after adjusting selected covariates, the results of multiple linear regression model showed that the MoCA score changed by −0.020 (95%CI: −0.035 - −0.005) for every 1 μg·L−1 increase of plasma Σ12PAHs. Low (<P33), medium ( P33~P66) and high (>P66) dummy variables were set according to the intertertile boundaries (8.31, 23.76) μg·L−1 of the plasma level of Σ12PAH of the workers. The change of MoCA score in the high concentration group versus the low concentration group was −1.167 (95%CI: −1.866 - −0.467). The MoCA score changed by 0.066 (95%CI: 0.012 - 0.119) for each 1 μg·L−1 increase in plasma BDNF level. The results of dichotomous logistic regression analysis showed that the risk of cognitive impairment in the high concentration group was 2.635 (95% CI: 1.085 - 6.398) times higher than that in the low concentration group. The results of mediating effect analysis showed that plasma BDNF level was an intermediate variable between PAHs and cognitive impairment, and 45.50% of PAHs-induced cognitive impairment risk was mediated by reduced BDNF level.

    Conclusion The level of plasma PAHs in coke oven workers is negatively correlated with MoCA score, and PAHs may mediate cognitive impairment by reducing plasma BDNF level.

     

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