Increased permeability across the blood-nerve barrier of albumin glycated in vitro and in vivo from patients with diabetic polyneuropathy.
Increased permeability across the blood-nerve barrier of albumin glycated in vitro and in vivo from patients with diabetic polyneuropathy.
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DOI：
10.1073/pnas.89.6.2218
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发表时间：
1992-03
影响因子：
11.1
通讯作者：
J. Poduslo;G. Curran
中科院分区：
文献类型：
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作者：
J. Poduslo;G. Curran
通过测定正常成年大鼠坐骨神经血-神经屏障对放射性碘标记白蛋白的渗透系数-表面积乘积（PS），研究了D-葡萄糖糖化人血浆白蛋白的血-神经转运。用CM-Affi-Gel Blue亲和层析法从正常人中分离人白蛋白（ALB），体外糖化1、3、10、19和30周。通过硼酸盐亲和色谱法将糖化ALB（gALB）与非糖化形式分离。通过[14 C]葡萄糖糖化的ALB的色谱法和放射性碘标记后分离的ALB和gALB的再色谱法来评估这种分离的效率。gALB也显示出具有较高的分子量，并且在Tris硼酸盐/EDTA缓冲液中SDS/孔梯度电泳后与ALB完全分离。糖化1周后，gALB PS是ALB PS的2.2倍。（0.724 +/- 0.063 x 10（-6）vs. 0.328 +/- 0.053 x 10（-6）ml.g-1.s-1;平均值+/- SD; P <0.0001），并随着糖化时间的增加而增加，在30周时达到最大值16.2倍（4.656 +/- 1.117 x 10（-6）vs. 0.288 +/- 0.042 x 10（-6）ml.g-1.s-1;平均值+/- SD; P小于0.0001）。未观察到残余神经内膜血浆量的变化。此外，与从相同患者分离的ALB的PS相比，从糖尿病性多发性神经病患者分离的gALB的PS显著增加（P <0.0001）。据推测，gALB和可能的其他糖化血清组分穿过血-神经屏障的渗透性增加，以及在糖尿病性多发性神经病患者的腓肠神经活检中观察到的ALB、IgG和IgM的定量增加，通过可能涉及神经微环境中的渗透性变化的机制，在长时间内促成糖尿病性多发性神经病的发展，糖化大分子对神经内膜内细胞的直接毒性作用，或由于糖化免疫球蛋白在神经内的捕获而通过经典免疫机制引起的神经损伤。
The blood-nerve transfer of human plasma albumin glycated with D-glucose was investigated by measuring the permeability coefficient-surface area product (PS) of the blood-nerve barrier to radioiodinated albumin in normal adult rat sciatic nerve. Human albumin (ALB) from normal individuals, freshly isolated by CM-Affi-Gel Blue affinity chromatography, was glycated in vitro for 1, 3, 10, 19, and 30 weeks. Glycated ALB (gALB) was separated from the nonglycated form by boronate-affinity chromatography. The efficiency of this separation was assessed by chromatography of ALB glycated with [14C]glucose and by rechromatography of isolated ALB and gALB after radioiodination. The gALB was also shown to have a higher molecular weight and be completely separated from ALB after SDS/pore gradient electrophoresis in a Tris borate/EDTA buffer. After 1 week of glycation, the gALB PS was 2.2-fold greater than the ALB PS (0.724 +/- 0.063 x 10(-6) vs. 0.328 +/- 0.053 x 10(-6) ml.g-1.s-1; mean +/- SD; P less than 0.0001) and it increased with the time of glycation reaching a maximum value of 16.2-fold greater at 30 weeks (4.656 +/- 1.117 x 10(-6) vs. 0.288 +/- 0.042 x 10(-6) ml.g-1.s-1; mean +/- SD; P less than 0.0001). No change was observed in the residual endoneurial plasma volume. In addition, the PS of gALB isolated from patients with diabetic polyneuropathy was significantly increased (P less than 0.0001) compared to the PS for ALB isolated from the same patients. It is hypothesized that the increased permeability of gALB and presumably other glycated serum components across the blood-nerve barrier, as well as the observed quantitative increase in ALB, IgG, and IgM in sural nerve biopsies from patients with diabetic polyneuropathy contribute to the development of diabetic polyneuropathy over a prolonged period of time by mechanisms that might involve osmotic changes in the nerve microenvironment, direct toxic effects of glycated macromolecules on cells within the endoneurium, or nerve damage by classical immunological mechanisms due to trapping of glycated immunoglobulins within nerve.