数字中医药(英文)2023,Vol.6Issue(3):317-327,11.DOI:10.1016/j.dcmed.2023.10.007
基于AGEs/RAGE/NF-κB通路探讨补肝散改善D-半乳糖致衰大鼠学习记忆障碍机制研究
Mechanism of Bugansan Decoction in ameliorating learning and memory impairment in D-galactose-induced aging rats based on AGEs/RAGE/NF-κB pathway
摘要
Abstract
Objective To investigate the underlying mechanism of the compound Bugansan Decoction(补肝散,BGSD)in intervening learning and memory in D-galactose(D-gal)-induced aging rats. Methods A total of 40 rats were randomly assigned to four groups:control,model,BGSD[14.06 g/(kg·d)],and piracetam[0.4 g/(kg·d)]groups,with 10 rats in each group.D-gal[400 mg/(kg·d)]was injected intraperitoneally to establish the aging rat model.The rats'body weight,water intake,food intake,and gripping strength were recorded each week.The eight-arm maze and step-down test were used to measure the rats'capacity for learning and memo-ry.Liver,thymus,spleen,and brain tissues were weighed to calculate the corresponding or-gan indices;serum malondialdehyde(MDA)content and superoxide dismutase(SOD)activi-ty were measured.Hematoxylin and eosin(HE)staining was adopted to observe the patholog-ical changes of the hippocampus;enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of tumor necrosis factor(TNF)-α,interleukin(IL)-6,and IL-1β in the hip-pocampus.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression of receptors for advanced glycation end products(RAGE),nuclear factor-κB(NF-κB),TNF-α,IL-6,and IL-1β mRNA in the hippocampus.Western blot(WB)was em-ployed to detect the expression levels of advanced glycation end products(AGEs),RAGE,and NF-κB protein in the hippocampus. Results In D-gal-induced aging rats,BGSD significantly increased food intake,water intake,body weight,gripping strength,and organ indices(P<0.05),and significantly decreased working memory error(WME),reference memory error(RME),and total memory errors(TE)in an eight-arm maze(P<0.05).In the step-down test,step-down latency was prolonged and the frequency of errors dropped(P<0.05).Additionally,BGSD could lessen the harm done to hippocampus neurons,increase serum SOD activity,lower MDA levels,and down-regulate the expression levels of the pro-inflammatory molecules TNF-α,IL-6,and IL-1β(P<0.05).Further findings showed that BGSD significantly decreased hippocampal AGEs,RAGE,and NF-κB expression(P<0.05). Conclusion By blocking the AGEs/RAGE/NF-κB signaling pathway,BGSD may regulate the neuroinflammatory damage in D-gal-induced aging rats,and thus improve learning and memory.关键词
补肝散/肝气虚/衰老/学习记忆/神经炎症/AGEs/RAGE/NF-κB信号通路Key words
Bugansan Decoction(补肝散,BGSD)/Liver Qi deficiency/Aging/Learning and memory/Neuroinflammation/AGEs/RAGE/NF-κB signaling pathway引用本文复制引用
李伟,王硕,王杰鹏,方芳,方朝义..基于AGEs/RAGE/NF-κB通路探讨补肝散改善D-半乳糖致衰大鼠学习记忆障碍机制研究[J].数字中医药(英文),2023,6(3):317-327,11.基金项目
Scientific Research Project of Hebei Administration of Traditional Chinese Medicine(2020136),and Science Research Project of Hebei Education Department(ZD2022043). (2020136)