Regulation of autophagy by the nuclear factor K b signaling pathway in the hippocampus of rats with

• 作 者: YunJie Su Yi Qu FengYan Zhao HuaFeng Li DeZhi Mu XiHong Li
• 出 处: 中国医师协会第一次全国儿童重症医师大会
• 发表日期: 2015年9期
• 关键词: sepsis brain damage autophagy NF-κB PDTC

　　Background Brain dysfunction is a serious symptom of sepsis and contributes to an increased risk of morbidity and mortality.Crosstalk between autophagy and NF-κB, two stress-response signaling pathways, has been detected in some pathophysiological processes.However, the process of autophagy in the hippocampus of septic rats and the role played by NF-κB in the regulation of autophagy during this process remains unknown.Methods Male Wistar rats were subjected to cecal ligation and puncture (CLP) or a sham operation.At 2 h before the CLP operation, rats were treated with pyrrolidine dithiocarbamate (PDTC), which is an inhibitor of the NF-κB signaling pathway, or a vehicle control.Following surgery, the morphological and physiological signs of brain dysfunction were measured.Autophagosome formation and lysosome activation were observed in the brain after CLP using an electron microscope.Western blotting and immune histochemistry were used to detect the cerebral levels of NF-κB and essential proteins involved in formation of the autophagosome (LC3, Beclin1, Lamp1 and Rab7).Results Compared with sham-operated rats, the CLP rats showed decreasing mean arterial pressure (MAP), increasing heart rate (HR), and pathological histological changes;CLP rats also exhibited an increased vacuolization by Electron Micrograph.This was consistent with the immunofluorescence and western blot finding that septic rats displayed an increase in the level of LC3-Ⅱin the CLP group, while Beclin1, LAMP1 and Rab7showed a decrease in later time in CLP groups.Inhibition of the NF-κB signal axis by PDTC blocked hippocampal NF-κB activation, increased the levels of LC3-Ⅱ , Beclin1, LAMP1 and Rab7, and improved physiological function (e.g., blood pressure and heart rate).Conclusions The autophagy process was blocked and NF-κB signaling pathway was activated;the inhibition of NF-κB signaling pathway stimulates autophagy in rats and the blockage of autophagy may contribute to septic brain damage.