Association of Exposure to Metal Fume Particulate Matter with Advanced Glycation End Products and Advanced Glycation End Products Receptor in Shipyard Welders

• Main Authors: LO, FU-YU, 羅富宇
• Other Authors: Lai, Ching-Huang
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/k2kq46

碩士 === 國防醫學院 === 公共衛生學研究所 === 107 === Background： Shipyard welders will expose to particulate matter and metal fumes through the routes of inhalation and ingestion during the welding process . In the past, it was found that the particles and metal fumes produced by the welding process can induce free radicals which could cause the oxidative stress and eventually lead to the formation of an inflammatory reaction. The interaction of advanced glycation end products (AGEs) and receptors of Advanced Glycation End Products (RAGE) can cause cellular effects, such as apoptosis and inflammation. In addition to cellular effects, it also relates health effects such as diabetes, kidney disease, neuropathy, and cancer. The soluble Receptors for Advanced Glycation End products (soluble RAGE, sRAGE) can be used as a decoy receptor to bind to AGEs, avoiding the inflammatory reaction caused by the binding of AGEs to the receptor of Advanced Glycation End Products (RAGE) on the cell surface. Though our previous cross-sectional study has confirmed that metal fumes exposure was positively associated with AGEs and RAGE. No any longitudinal study has been confirmed the relationship between particulate matter and metal fumes exposure and AGEs and RAGE. Objectives： 1. To explore the relationship between the biomarkers of exposure to metals and AGEs, RAGE, sRAGE. 2. To explore the relationship among AGEs, RAGE, sRAGE and inflammatory markers. 3. To explore the relationship among AGEs, RAGE, sRAGE and insulin resistance. Methods： The study was conducted in both a cross-sectional and longitudinal study designs. Study subjects consisted of 53 welders and 29 office workers at baseline from a shipyard of northern Taiwan in 2018 and consisted 73 welders and 27 office workers in 2019 follow-up. Participants were asked to wear PM2.5 samplers during their working hours on the first weekday (Monday) and collected urine and fasting blood samples on the next day (Tuesday) morning. Monocytic receptor of advanced glycation end products expression was assessed flow cytometry. AGEs, IL-6, TNF-α were analyzed by ELISA kits. Urinary metal concentration was analyzed by (Inductively coupled plasma mass spectrometry) ICP- MS. Statistical analysis was conducted using SPSS 22.0.Study subjects was a shipyard worker of northern Taiwan, including internal staff, dock personnel and administrative staff, excluding female subjects, and the number of people receiving the case was 100. Participants wore a personal sampler before work to measure PM2.5 exposure concentrations for 8 hours of a day. On the second day, collect basic personal parameters (height, weight, waist circumference, hip circumference), urinary biochemical value, blood biochemical value, and questionnaires such as subjects living habits, work status, and diet status during physical examination. Urinary metal concentration was analyzed by ICP-MS (Inductively coupled plasma mass spectrometry). Results： In the linear regression analysis, after adjusting for urinary creatinine and smoking habits, urinary manganese (β=0.279, p=0.006), iron (β=0.273, p=0.007) and lead (β=0.290, p=0.005) were individual positively associated with AGEs. In addition, urinary chromium (β=0.270, p=0.012), manganese (β=0.239, p=0.029) and iron (β=0.232, p=0.033) were individual positively associated with RAGE. Linear regression analysis of AGEs and RAGE with inflammatory factors (IL-6, TNF-α), AGEs (β=0.234, p=0.024), RAGE (β=0.227, p=0.033) and sRAGE (β=0.267, p=0.007) were individual positively associated with TNF-α after adjusting group. In the generalized estimation equation analysis, after adjusting for time, urinary creatinine, smoking habits and age, PM2.5 (β=0.168, p=0.006), urinary nickel (β=0.210, p<0.001), zinc (β=0.323, p=0.012) and iron (β=0.233, p=0.011) were individual positively associated with AGEs. In addition, PM2.5 (β=0.190, p=0.008), urinary chromium (β=0.356, p< 0.001), manganese (β=0.417, p=0.043), nickel (β=0.165, p=0.003) and cadmium (β=0.160, p=0.004) were also individual positively associated with RAGE after adjusting time, age, smoking habits. AGEs (β=0.172, p=0.013) was positive associated with HOMA-IR after adjusting time, age, smoking habits and BMI. Conclusion： Urinary manganese, iron and lead are individual positively associated with AGEs. Urinary chromium, manganese and iron are individual positively associated with RAGE. RAGE is positively associated with IL-6. AGEs, RAGE, sRAGE are individual positively associated with TNF-α. In the longitudinal study, we conclude that exposure to welding fume particles is associated with increasing AGEs levels and RAGE expression. AGEs level is associated with increased HOMA-IR. Keywords：welding fume particle, urinary metals, Advanced Glycation End Products (AGEs), Receptors of Advanced Glycation End Products (RAGE), soluble Receptors for Advanced Glycation End products (sRAGE), IL-6, TNF-α, insulin resistance.