Department of Pathophysiology, Key Laboratory of Cell Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Department of Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030013, P.R. China.
Mol Med Rep. 2017 Aug;16(2):1878-1884. doi: 10.3892/mmr.2017.6780. Epub 2017 Jun 15.
The present study aimed to investigate the effects of intestinal endotoxemia (IETM) in a rat model of aluminum neurotoxicity established by D-galactose and aluminum trichloride (AlCl3). Adult Wistar rats were administered D‑galactose and AlCl3 to create the aluminum neurotoxicity model. The learning and memory abilities of the rats were subsequently observed using a Morris water maze test and the serum levels of lipopolysaccharide (LPS), tumor necrosis factor (TNF)‑α, interleukin (IL)‑1, diamine oxidase (DAO), glutamine (Gln) and glutaminase were measured. The expression of S‑100β in the serum was detected using an enzyme‑linked immunosorbent assay. The expression levels of the amyloid β‑protein (Aβ) precursor (APP), presenilin 1 (PS1), β‑site APP‑cleaving enzyme (BACE), zona occludens protein (ZO)‑1 and Aβ 1‑40 in the brain of rats were detected via reverse‑transcription polymerase chain reaction, western blotting and immunohistochemistry. The levels of LPS, TNF‑α, IL‑1, DAO, Gln and S‑100β in serum and the mRNA and protein expression levels of APP, PS1, BACE and Aβ1‑40 in the brain were markedly increased in the model rats compared with controls. The level of glutaminase in the serum and the expression of ZO‑1 in the brain were decreased in the model rats compared with controls. IETM was present in the rat model of aluminum neurotoxicity established by D‑galactose and AlCl3 and may be important in the development of this neurotoxicity.
本研究旨在探讨肠内内毒素血症（IETM）在 D-半乳糖和三氯化铝（AlCl3）建立的大鼠铝神经毒性模型中的作用。成年 Wistar 大鼠给予 D-半乳糖和 AlCl3 建立铝神经毒性模型。随后，使用 Morris 水迷宫测试观察大鼠的学习和记忆能力，测量血清中脂多糖（LPS）、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1、二胺氧化酶（DAO）、谷氨酰胺（Gln）和谷氨酰胺酶的水平。酶联免疫吸附试验检测血清中 S-100β 的表达。通过逆转录聚合酶链反应、western blot 和免疫组织化学检测大鼠脑内淀粉样β-蛋白（Aβ）前体（APP）、早老素 1（PS1）、β-位点 APP 裂解酶（BACE）、闭合蛋白（ZO）-1 和 Aβ1-40 的表达水平。与对照组相比，模型组大鼠血清中 LPS、TNF-α、IL-1、DAO、Gln 和 S-100β 的水平以及脑内 APP、PS1、BACE 和 Aβ1-40 的 mRNA 和蛋白表达水平明显升高。与对照组相比，模型组大鼠血清中谷氨酰胺酶的水平和脑内 ZO-1 的表达降低。D-半乳糖和 AlCl3 建立的大鼠铝神经毒性模型存在 IETM，这可能是神经毒性发生的重要因素。
