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长期砷暴露引起的血脑屏障破坏与 MMP-9 和 MMP-2 的增加有关:其特征与衰老引起的特征相似。

The disruption of blood-brain barrier induced by long-term arsenic exposure is associated with the increase of MMP-9 and MMP-2: The characteristics are similar to those caused by senescence.

机构信息

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Baojian Road, Harbin, 150081, Heilongjiang Province, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of PR China, Harbin Medical University, Baojian Road, Harbin, 150081, Heilongjiang Province, China.

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Baojian Road, Harbin, 150081, Heilongjiang Province, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of PR China, Harbin Medical University, Baojian Road, Harbin, 150081, Heilongjiang Province, China.

出版信息

Chem Biol Interact. 2023 Nov 1;385:110743. doi: 10.1016/j.cbi.2023.110743. Epub 2023 Oct 5.

Abstract

Accumulating evidence suggests that Matrix metalloproteinase-9 (MMP-9) and -2 (MMP-2) are involved in the neuropathological processes by contributing to breaking the extracellular matrix and the tight junctions that constitute the blood-brain barrier (BBB). However, the influences of arsenic (As) on these two MMPs were inconsistent. In the cross-sectional study of 500 adults, serum MMP-2 and MMP-9 positively correlated with urine arsenic. And the positive correlation between urine tAs and serum MMP-9/2 was found in people older than 59 years. In vivo studies, we found that arsenic exposure or senescence might decrease number of neurons and neuritic density and increase serum and cortical MMP-9/2 levels. Furthermore, arsenic exposure or senescence could disrupt the tight junction of BBB and elevate MMP-9 and MMP-2 expression in the cerebral microvascular endothelium. The MMP-9 and MMP-2 are of particular interest when researching the link between arsenic exposure and nerve damage.

摘要

越来越多的证据表明,基质金属蛋白酶-9(MMP-9)和 -2(MMP-2)通过破坏细胞外基质和构成血脑屏障(BBB)的紧密连接,参与神经病理学过程。然而,砷(As)对这两种 MMP 的影响并不一致。在对 500 名成年人的横断面研究中,血清 MMP-2 和 MMP-9 与尿砷呈正相关。在年龄大于 59 岁的人群中,发现尿总砷与血清 MMP-9/2 之间存在正相关。体内研究发现,砷暴露或衰老可能会减少神经元数量和神经突密度,并增加血清和皮质 MMP-9/2 水平。此外,砷暴露或衰老可破坏 BBB 的紧密连接,并增加脑微血管内皮细胞中 MMP-9 和 MMP-2 的表达。在研究砷暴露与神经损伤之间的联系时,MMP-9 和 MMP-2 特别值得关注。

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