Lanthanum Chloride Impairs the Blood-Brain Barrier Integrity by Reduction of Junctional Proteins and Upregulation of MMP-9 in Rats

被引：25
作者：
Wu, Jie [1 ,2 ]
Yang, Jinghua [1 ]
Lu, Xiaobo [1 ]
Jin, Cuihong [1 ]
Wu, Shengwen [1 ]
Zhang, Lijin [1 ]
Hu, Xiaoyu [1 ]
Ma, Honglin [2 ]
Cai, Yuan [1 ]
机构：
[1] China Med Univ, Sch Publ Hlth, Dept Toxicol, 77 Puhe Rd, Shenyang 110122, Liaoning, Peoples R China
[2] Jinzhou Med Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, 40 Sect Three Songpo Rd, Jinzhou 121001, Peoples R China
来源：
BIOLOGICAL TRACE ELEMENT RESEARCH | 2019年 / 187卷 / 02期
基金：
中国国家自然科学基金;
关键词：
Lanthanum; Blood-brain barrier; Tight junctions; Matrix metalloproteinases; MATRIX METALLOPROTEINASES; ENDOTHELIAL ADHERENS; CEREBRAL-ISCHEMIA; TIGHT JUNCTIONS; TERM EXPOSURE; PERMEABILITY; REPERFUSION; HIPPOCAMPUS; DISRUPTION; MEMORY;
D O I：
10.1007/s12011-018-1402-2
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Lanthanum could cause cognitive impairment in children and rodent animals. The normal blood-brain barrier (BBB) integrity is essential for protecting the brain from systemic toxins and maintaining the homeostasis for proper neuronal function. BBB dysfunction has been implicated as a potential mechanism of heavy metal-induced neurotoxicity. The present study was aimed to investigate effects of lanthanum on BBB integrity and endothelial junctional complexes in the cerebral cortex of young rats. Animals were exposed to lanthanum chloride (LaCl3) through drinking water under 0, 0.25, 0.5, and 1.0% concentrations from postnatal day 0 until 30days after weaning. LaCl3-exposure increased BBB permeability, caused ultrastructure changes in cerebral capillaries, and reduced protein expression of claudin-5, occludin, and VE-cadherin. Due to the critical role of matrix metalloproteinases (MMPs) in BBB integrity, we further examined alterations in MMPs activity and expression. Enhanced gelatinase activity and upregulated MMP-9 expression were observed after LaCl3-exposure, concurrently with decreased expression of endogenous inhibitor tissue inhibitors of metalloproteinase (TIMP)-1. Taken together, this study demonstrated that postnatal lanthanum exposure caused leakage of BBB in young rats, partially attributed to upregulation of MMP-9 and reduction of junctional proteins expression.
引用
收藏
页码：482 / 491
页数：10
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