中老年人群除草剂暴露与肝酶水平的关联

Association between herbicide exposure and liver enzyme levels in a middle-aged and elderly population

  • 摘要:
    背景 除草剂的广泛使用导致环境污染,并对人类健康产生影响。肝脏是环境污染物解毒的重要器官,但目前关于除草剂暴露与肝功能关系的研究有限。
    目的 探究中老年人基线血清除草剂浓度与5年间肝酶水平变化值及肝酶异常的关联。
    方法 本研究基于东风-同济队列中的糖尿病巢式病例-对照人群,共纳入1388名研究对象,5年后随访一次。通过问卷调查收集流行病学资料,采用气相色谱-质谱联用仪检测基线血清中异丙甲草胺、苯胺灵和乙草胺的浓度。基线和随访时检测血清谷草转氨酶(AST)和谷丙转氨酶(ALT)水平。将除草剂浓度以四分位分组,使用线性回归模型评估基线血清除草剂浓度与5年内AST和ALT变化值的关联,校正年龄、性别、教育水平、吸烟状况、饮酒状况、体育锻炼、体质量指数和随访时是否新发2型糖尿病。采用logistic回归模型分析基线血清除草剂浓度与随访时肝酶异常发生风险的关联。
    结果 异丙甲草胺、苯胺灵和乙草胺检出率均高于80%,加标回收率为73.46%~106.77%。基线时研究对象的年龄为(62.7±7.6)岁,男性占比34.1%,血清异丙甲草胺、苯胺灵和乙草胺的平均浓度(中位数)分别为0.05、0.16、0.03 ng·mL−1。3种血清除草剂基线浓度在随访时肝酶正常(n=1297)和异常(n=91)两组间差异无统计学意义(P >0.05)。肝酶异常组的基线肝酶水平较高,且5年间AST和ALT的变化值高于肝酶正常组(P <0.05)。线性回归分析显示:与最低分位组相比,苯胺灵的第二、三、四分位组的AST变化值呈逐渐增加的趋势(第二分位:b=1.49,95%CI:0.10~2.87;第三分位:b=1.52,95%CI:0.14~2.90;第四分位:b=1.69,95%CI:0.31~3.08;P <0.05)。异丙甲草胺和乙草胺浓度与AST变化值的关联无统计学意义。未发现3种除草剂与ALT 5年内变化值及肝酶异常发生风险之间存在关联。
    结论 在中老年人群中,随着血清苯胺灵浓度增加,肝酶AST水平的变化值增加,可能对肝功能产生影响。未来仍需更多研究为发现除草剂暴露与肝功能的关联提供科学证据。

     

    Abstract:
    Background The widespread use of herbicides has led to environmental contamination and has implications for human health. The liver is an important organ for the detoxification of environmental pollutants; however, studies on the association between herbicide exposure and liver function are limited.
    Objectives To investigate the association between baseline serum herbicide levels and changes in liver enzyme levels and liver enzyme abnormalities over a 5-year period in middle-aged and older adults.
    Methods This study was based on a nested case-control population of type 2 diabetes established in the Dongfeng-Tongji cohort, with a total of 1388 subjects included in this study and followed up for 5 years. Epidemiological data were collected through questionnaires, and baseline serum concentrations of three herbicides (metolachlor, propham, and acetochlor) were measured by gas chromatography-triple quadrupole mass spectrometry. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were detected at baseline and follow-up visits. The associations between baseline serum herbicide levels and changes in AST and ALT over 5 years were assessed using linear regression models with herbicide levels categorized into quartiles, adjusting for age, sex, education level, smoking status, drinking status, physical activity, body mass index, and new-onset type 2 diabetes occurred during follow-up. The relationship between baseline serum herbicide levels and the risk of liver enzyme abnormalities during follow-up was further analyzed using logistic regression models.
    Results The positive rates of metolachlor, propham, and acetochlor were all higher than 80%, and their spiked rates of recovery ranged from 73.46% to 106.77%. The mean ± standard deviation of the age of subjects at baseline was (62.7±7.6) years, with 34.1% being male. The median serum levels of metolachlor, propham, and acetochlor at baseline were 0.05, 0.16, and 0.03 ng·mL−1, respectively. There was no significant difference in baseline serum herbicide levels between the normal and abnormal liver enzyme groups at follow-up (P >0.05). The baseline liver enzyme levels and the changes in AST and ALT over 5 years in those who developed abnormal liver enzymes were significantly higher than those in the normal liver enzyme group (P <0.05). The linear regression analysis showed that the changes in AST increased progressively over 5 years in the second, third, and fourth quartiles of propham compared to the lowest quartile group (the second quartile: b=1.49, 95%CI: 0.10, 2.87; the third quartile: b=1.52, 95%CI: 0.14, 2.90; the fourth quartile: b=1.69, 95%CI: 0.31, 3.08; P <0.05). The associations of serum metolachlor and acetochlor with changes in AST were not significant. Additionally, no significant relationships were found between the three serum herbicides and the changes in ALT over 5 years or the risk of liver enzyme abnormalities.
    Conclusion Serum propham levels in middle-aged and older adults are positively associated with changes in liver enzyme AST, which may have an effect on liver function. More studies are needed to provide scientific evidence for the association between herbicide exposure and liver function.

     

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