Tian Jing, Dai Hongmei, Deng Yuanying, Zhang Jie, Li Ying, Zhou Jun, Zhao Mingyi, Zhao Mengwen, Zhang Chen, Zhang Yuxi, Wang Peipei, Bing Guoying, Zhao Lingling
Department of Pediatrics, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
Toxicology. 2015 Dec 2;338:95-103. doi: 10.1016/j.tox.2015.10.010. Epub 2015 Oct 30.
Chlorpyrifos (CPF), one of organophosphorus pesticides (OPs), is associated with developmental neurotoxicity. Inflammatory response is closely related with CPF-induced neurotoxicity. The present study aimed at exploring whether sub-toxic CPF exposure on neonatal rats results in neuroinflammation that mediated by HMGB1/TLR4/NF-κB signaling pathway in the amygdala. The neonatal rats were subcutaneously injected with 5mg/kg CPF for 4 consecutive days (postnatal day 11-14) with or without HMGB1 inhibitor, glycyrrhizin. We assessed the levels of pro-inflammatory cytokines at 12, 24, and 72 h after CPF exposure. The role of HMGB1 on neuroinflammation in sub-toxic exposure during brain development was studied. CPF-treated neonatal rats exhibited a significant increase in the expression of pro-inflammatory cytokines, such as IL-6, TNF-α and HMGB1, and a significant increase in the activation of NF-κB in the amygdala after CPF exposure. Inhibited HMGB1 reduced the release of IL-6 and TNF-α, and inhibited activation of NF-κB. Our findings indicate that CPF exposure on developmental brain might induce the activation of neuroinflammation mediated by HMGB1/TLR4/NF-κB pathway in the amygdala.
毒死蜱（CPF）是有机磷农药（OPs）之一，与发育性神经毒性有关。炎症反应与CPF诱导的神经毒性密切相关。本研究旨在探讨新生大鼠亚毒性暴露于CPF是否会导致杏仁核中由HMGB1/TLR4/NF-κB信号通路介导的神经炎症。新生大鼠连续4天（出生后第11 - 14天）皮下注射5mg/kg CPF，同时或不同时给予HMGB1抑制剂甘草甜素。我们在CPF暴露后12、24和72小时评估促炎细胞因子水平。研究了HMGB1在脑发育亚毒性暴露期间对神经炎症的作用。CPF处理的新生大鼠在CPF暴露后杏仁核中促炎细胞因子如IL-6、TNF-α和HMGB1的表达显著增加，NF-κB的激活也显著增加。抑制HMGB1可减少IL-6和TNF-α的释放，并抑制NF-κB的激活。我们的研究结果表明，发育中的大脑暴露于CPF可能会诱导杏仁核中由HMGB1/TLR4/NF-κB途径介导的神经炎症激活。
