Transthyretin, thyroxine, and retinol-binding protein in human cerebrospinal fluid: effect of lead exposure.
Transthyretin, thyroxine, and retinol-binding protein in human cerebrospinal fluid: effect of lead exposure.
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DOI：
10.1093/toxsci/61.1.107
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发表时间：
2001-05
期刊：
影响因子：
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通讯作者：
Wei Zheng;Yong-Ming Lu;G. Lu;Qiuqu Zhao;Onpan Cheung;W. Blaner
中科院分区：
文献类型：
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作者：
Wei Zheng;Yong-Ming Lu;G. Lu;Qiuqu Zhao;Onpan Cheung;W. Blaner
甲状腺素运载蛋白（TTR），由脉络丛合成，被认为在脑中甲状腺激素的运输中起作用。我们以前的动物研究表明，铅（Pb）在脉络丛隔离可能会导致脑脊液（CSF）中TTR水平显着下降。本研究的目的是确定人类脑脊液中TTR和甲状腺素（T（4））是否相关，以及脑脊液中Pb水平是否与TTR、T（4）和/或视黄醇结合蛋白（RBP）相关。从接受CSF化学临床诊断的患者中采集了82对CSF和血液/血清样本。结果显示，TTR的CSF浓度平均值为3.33 +/- 1.60 μ g/mg CSF蛋白（平均值+/- SD，n = 82），总T（4）（TT（4））为1.56 +/- 1.68 ng/mg（n = 82），RBP为0.34 +/- 0.19 μ g/mg（n = 82），铅为0.53 +/- 0.69微克/分升（高于检测限的为61例）。线性回归分析显示，脑脊液TTR水平与脑脊液TT（4）水平呈正相关（r = 0.33，p < 0.005）。然而，CSF TTR浓度与CSF Pb浓度呈负相关（r =-0.29，p < 0.05）。CSF TT（4）和CSF Pb浓度之间存在反向相关性（r =-0.22，p = 0.09），但相关性较弱。脑脊液中TTR、TT（4）和Pb的浓度不随血液或血清中TTR、TT（4）和Pb浓度的变化而变化，但脑脊液中RBP浓度与血清中的浓度相关（r = 0.39，p < 0.0005）。与TTR不同，CSF RBP浓度不受PB的影响：这些人体数据与我们早期在动物中的观察结果一致，这表明TTR是CSF中甲状腺素转运所必需的，铅暴露可能与CSF中TTR水平降低相关。
Transthyretin (TTR), synthesized by the choroid plexus, is proposed to have a role in transport of thyroid hormones in the brain. Our previous studies in animals suggest that sequestration of lead (Pb) in the choroid plexus may lead to a marked decrease in TTR levels in the cerebrospinal fluid (CSF). The objectives of this study were to establish in humans whether TTR and thyroxine (T(4)) are correlated in the CSF, and whether CSF levels of Pb are associated with those of TTR, T(4), and/or retinol-binding protein (RBP). Eighty-two paired CSF and blood/serum samples were collected from patients undergoing clinical diagnosis of CSF chemistry. Results showed that the mean value of CSF concentrations for TTR was 3.33 +/- 1.60 microg/mg of CSF proteins (mean +/- SD, n = 82), for total T(4) (TT(4)) was 1.56 +/- 1.68 ng/mg (n = 82), for RBP was 0.34 +/- 0.19 microg/mg (n = 82), and for Pb was 0.53 +/- 0.69 microg/dl (n = 61 for those above the detection limit). Linear regression analyses revealed that CSF TTR levels were positively associated with those of CSF TT(4) (r = 0.33, p < 0.005). CSF TTR concentrations, however, were inversely associated with CSF Pb concentrations (r = -0.29, p < 0.05). There was an inverse, albeit weak, correlation between CSF TT(4) and CSF Pb concentrations (r = -0.22, p = 0.09). The concentrations of TTR, TT(4), and Pb in the CSF did not vary as the function of their levels in blood or serum, but RBP concentrations in the CSF did correlate to those of serum (r = 0.39, p < 0.0005). Unlike TTR, CSF RBP concentrations were not influenced by PB: These human data are consistent with our earlier observations in animals, which suggest that TTR is required for thyroxine transport in the CSF and that Pb exposure is likely associated with diminished TTR levels in the CSF.