Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Chemosphere. 2018 Jul;203:170-178. doi: 10.1016/j.chemosphere.2018.03.162. Epub 2018 Mar 27.
Aluminum (Al) is a recognized environmental pollutant that causes neuroinflammatory lesions, leading to neurodegenerative diseases. Interleukin-1 (IL-1) signaling pathway is responsible for regulating inflammatory lesions. However, it remains unclear whether IL-1 signaling pathway is involved in neuroinflammatory lesions induced by Al exposure. In the present study, one hundred and twenty Wistar rats were orally exposed to 0, 50, 150 and 450 mg/kg BW/d aluminum trichloride (AlCl) for 90 days, respectively. We found that AlCl exposure increased hippocampal Al concentration, reduced hippocampus coefficient, impaired cognitive ability, deteriorated microstructure of hippocampal CA1 and CA3 regions, increased reactive oxygen species (ROS) level, activated astrocytes and microglia, increased pro-inflammatory cytokines contents and mRNA expressions, and decreased anti-inflammatory cytokines contents and mRNA expressions in the hippocampus. These results indicated that AlCl induced the hippocampal inflammatory lesion (HIL). Moreover, AlCl exposure increased the mRNA and protein expression of IL-1 signaling pathway core components in the hippocampus, demonstrating that AlCl activated IL-1 signaling pathway. Furthermore, the correlation between interleukin-1β (IL-1β) content and HIL and activation of the IL-1 signaling pathway was analyzed. Results showed that IL-1β content was positively correlated with pro-inflammatory cytokines contents and mRNA expressions and activation of IL-1 signaling pathway, and was negatively correlated with hippocampus coefficient, anti-inflammatory cytokines contents and mRNA expressions, and the number of hippocampal neurons. The above results demonstrate that AlCl-induced HIL is associated with IL-1 signaling pathway, in which IL-1β is a link.
铝（Al）是一种公认的环境污染物，可导致神经炎症病变，进而引发神经退行性疾病。白细胞介素-1（IL-1）信号通路负责调节炎症病变。然而，目前尚不清楚 IL-1 信号通路是否参与了铝暴露引起的神经炎症病变。在本研究中，将 120 只 Wistar 大鼠分别经口暴露于 0、50、150 和 450mg/kg BW/d 三氯化铝（AlCl）90 天。结果发现，AlCl 暴露增加了海马区的铝浓度，降低了海马区系数，损害了认知能力，破坏了海马 CA1 和 CA3 区的微观结构，增加了活性氧（ROS）水平，激活了星形胶质细胞和小胶质细胞，增加了促炎细胞因子的含量和 mRNA 表达，降低了海马区抗炎细胞因子的含量和 mRNA 表达。这些结果表明 AlCl 诱导了海马炎症病变（HIL）。此外，AlCl 暴露增加了海马中 IL-1 信号通路核心成分的 mRNA 和蛋白表达，表明 AlCl 激活了 IL-1 信号通路。进一步分析了白细胞介素-1β（IL-1β）含量与 HIL 和 IL-1 信号通路激活之间的相关性。结果表明，IL-1β含量与促炎细胞因子的含量和 mRNA 表达以及 IL-1 信号通路的激活呈正相关，与海马区系数、抗炎细胞因子的含量和 mRNA 表达以及海马神经元数量呈负相关。上述结果表明，AlCl 诱导的 HIL 与 IL-1 信号通路有关，其中 IL-1β是一个关键分子。
