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儿童患者体内金属/类金属的血脑屏障通透性及其决定因素。

Blood-cerebrospinal fluid barrier permeability of metals/metalloids and its determinants in pediatric patients.

机构信息

Department of Clinical Laboratory, Guangdong Women and Children Hospital, Guangzhou, China.

Department of Preventive Medicine, School of Public Health, Guangzhou Medical University, Guangzhou, China.

出版信息

Ecotoxicol Environ Saf. 2023 Nov 1;266:115599. doi: 10.1016/j.ecoenv.2023.115599. Epub 2023 Oct 21.

Abstract

Concerns regarding adverse effects of metal/metalloids exposure on brain development and neurological disorders among children are increasing. However, the transport patterns of metals/metalloids across the blood-cerebrospinal fluid barrier (BCSFB) need to be clarified in children. A total of 99 Chinese pediatric patients were enrolled from February 2020 to August 2021, with a median age of 6.76 months. We detected 16 metal/metalloid levels in matched serum and cerebrospinal fluid (CSF) samples using inductively coupled plasma mass spectrometry. The BCSFB permeability of metals/metalloids were estimated and the potential effects of biomedical parameters were explored. Most metals/metalloids were detectable among > 80.0% of CSF samples. Significant correlations were observed between strontium (Sr, r = 0.46), molybdenum (Mo, r = 0.50), and cadmium (Cd, r = 0.24) concentrations in serum and CSF (P < 0.05). Ratios of metal/metalloid levels in CSF to serum (R) ranged from 0.02 to 0.74, and hazardous metals/metalloids including arsenic (As), Cd, lead (Pb), thallium (Tl), and manganese (Mn) showed high transfer efficiencies across the BCSFB (R > 0.5). With the adjustment of age and sex, albumin, β2-microglobulin, and total protein levels in CSF were positively associated with copper (Cu) permeability (FDR-adjusted P < 0.05), while glucose in CSF was negatively correlated with calcium (Ca), Cu, Sr, and Mo BCSFB permeability (FDR-adjusted P < 0.05). Q-Alb promoted Cu permeability across the BCSFB (FDR-adjusted P < 0.001), while C-reactive protein levels in serum were positively associated with selenium (Se) permeability (FDR-adjusted P = 0.046). For the first time, our findings provided data for the BCSFB permeability of 16 metals/metalloids in children, and indicated that some biomedical parameters could influence the transformation of metals/metalloids from serum to CSF. Metals/metalloids with strong BCSFB permeability warrant attention for their potential neurotoxicity.

摘要

人们越来越关注金属/类金属暴露对儿童大脑发育和神经发育障碍的不良影响。然而,金属/类金属跨血脑屏障(BCSFB)的转运模式仍需在儿童中阐明。本研究共纳入 2020 年 2 月至 2021 年 8 月期间的 99 例中国儿科患者,中位年龄为 6.76 个月。采用电感耦合等离子体质谱法检测配对血清和脑脊液(CSF)样本中的 16 种金属/类金属水平。估计了金属/类金属的 BCSFB 通透性,并探讨了生物医学参数的潜在影响。大多数金属/类金属在>80.0%的 CSF 样本中均可检测到。血清和 CSF 中锶(Sr,r=0.46)、钼(Mo,r=0.50)和镉(Cd,r=0.24)浓度之间存在显著相关性(P<0.05)。金属/类金属在 CSF 与血清中的比值(R)范围为 0.02 至 0.74,砷(As)、Cd、铅(Pb)、铊(Tl)和锰(Mn)等有害金属/类金属表现出较高的跨 BCSFB 转运效率(R>0.5)。在校正年龄和性别后,CSF 中的白蛋白、β2-微球蛋白和总蛋白水平与铜(Cu)通透性呈正相关(FDR 调整后 P<0.05),而 CSF 中的葡萄糖与钙(Ca)、Cu、Sr 和 Mo 的 BCSFB 通透性呈负相关(FDR 调整后 P<0.05)。Q-Alb 促进了 BCSFB 中 Cu 的通透性(FDR 调整后 P<0.001),而血清中的 C 反应蛋白水平与硒(Se)的通透性呈正相关(FDR 调整后 P=0.046)。本研究首次提供了儿童 16 种金属/类金属 BCSFB 通透性的数据,并表明一些生物医学参数可能会影响金属/类金属从血清向 CSF 的转化。具有较强 BCSFB 通透性的金属/类金属值得关注,因为它们可能具有神经毒性。

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