Increased amyloid β-peptide (1-40) level in brain of streptozotocin-induced diabetic rats
Increased amyloid β-peptide (1-40) level in brain of streptozotocin-induced diabetic rats
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DOI：
10.1016/j.neuroscience.2008.03.019
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发表时间：
2008-05-15
期刊：
影响因子：
3.3
通讯作者：
Wang, G.
中科院分区：
文献类型：
--
作者：
Liu, Y.;Liu, H.;Wang, G.
本研究的目的是研究糖尿病大鼠脑中淀粉样β肽（A β）（1-40）的水平是否增加，以及这种增加是否与血脑屏障P-糖蛋白功能障碍有关。通过腹膜内注射单次给予65 mg/kg链脲佐菌素诱导糖尿病样病症。采用酶联免疫吸附测定（ELISA）试剂盒测定糖尿病大鼠脑中A β（1-40）水平。分别使用脑外排指数和脑渗透系数-表面积乘积测量[I-125]标记的人淀粉样蛋白-p-肽（hA β）（1-40）的体内脑-血外排和血-脑内流转运。[C-14]菊糖用作参比化合物。结果显示，糖尿病大鼠颞叶皮层和海马A β（1-40）水平显著升高。糖尿病大鼠脑内微量注射125 I后30 min，脑内[（125）I]hA β（1-40）残留率显著增加，脑外排指数下降。P-糖蛋白抑制剂维拉帕米或环孢菌素A预处理显著增加[I-125]hA β（1-40）的脑残留百分比。糖尿病大鼠中[I-125]hA β（1-40）的脑渗透系数-表面积乘积增加，同时血浆中A β（1-40）水平增加。目前的研究表明，糖尿病状态可以增加脑中A β（1-40）的水平，这可能至少部分地解释为，由于糖尿病大鼠脑P-糖蛋白功能缺陷，A β（1-40）的脑-血流出量下降。(c)2008年IBRO。由爱思唯尔有限公司出版。保留所有权利。
The aims of the study were to investigate whether the level of amyloid beta-peptide (A beta) (1-40) was increased in brain of diabetic rats and whether the increase was associated with dysfunction of P-glycoprotein at the blood-brain barrier. A diabetes-like condition was induced by single administration of 65 mg/kg streptozotocin via i.p. injection. A beta (1-40) levels in brain of the diabetic rats were measured using an enzyme linked immunosorbent assay (ELISA) kit. The in vivo brain-to-blood efflux and blood-to-brain influx transport of [I-125]-labeled human amyloid-p-peptide (hA beta) (1-40) were measured using the brain efflux index and brain permeability coefficient-surface area product, respectively. [C-14]inulin served as a reference compound. The results showed that A beta (1-40) levels significantly increased in temporal cortex and hippocampus of the diabetic rats. The brain remaining percentage of [(125) I]hA beta (1-40) in diabetic rats significantly increased at 30 min after intracerebral microinjection, accompanied by decrease of the brain efflux index. Pretreatment of P-glycoprotein inhibitors verapamil or cyclosporin A significantly increased the brain remaining percentage of [I-125]hA beta (1-40). The brain permeability coefficient-surface area product of [I-125]hA beta (1-40) was increased in diabetic rats, accompanied by increased A beta (1-40) levels in plasma. The present study demonstrated that a diabetic state could increase A beta (1-40) levels in brain, which might be explained, at least in part, by the decline in brain-to-blood efflux of A beta (1-40) due to deficient cerebral P-glycoprotein function in diabetic rats. (c) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.