摘要
目的探讨淫羊藿总黄酮(EF)经由核因子-κB(NF-κB)家族相关信号转导途径调控免疫衰老的有效机制。方法(1)采用流式细胞仪监测老龄大鼠脾淋巴细胞凋亡率。(2)采用NF-κB信号通路基因芯片(96个相关基因),分别检测各组大鼠NF-κB相关信号差异表达,并提取其中有显著意义的主要分子,加以分析。结果(1)老年对照组大鼠普遍存在淋巴细胞过度凋亡现象,但EF组及联合组均可显著抑制这种过度凋亡状态。(2)EF干预后的基因芯片检测结果中,不同程度上调的有73个基因(其中NF-κB/Rel/IB家族成员10个),这些基因群覆盖了NIK/IKK/IB/Rel/NF-κB信号转导途径成员、NF-κB调控靶基因、跨膜受体、转录因子及其相关的受体蛋白等。通过NF-κB阻断剂二硫代氨基甲酸吡咯烷(PDTC)对NF-κB进行阻断,未发现NF-κB家族成员上调表达,其信号转导途径相关分子亦明显减少;而联合组NF-κB家族仍可不同程度活化相关转导途径。(3)EF和联合组对NF-κB家族的影响有明显的共同特点,即EF对于NF-κB1、NF-κB2、RelB、IBε的显著上调和对NIK/IKK/IB/Rel/NF-κB信号转导途径的激活。结论EF可抑制老年大鼠脾淋巴细胞过度凋亡、激活老年大鼠Rel/NF-κB/IB/IKK及其相关信号转导途径,最终经由IBε、IBα的调节,使NF-κB在适度范围上调,这可能是EF重建T淋巴细胞凋亡平衡免疫稳态、延缓免疫衰老的重要机制。
Objective To explore the mechanism of epimedium flavonoids （EF） in regulating immunosenescence via nuclear factor-kappa B （NF-κB） related signal transduction pathway. Methods （1） The apoptosis index （AI） of splenic lymphocyte in aged rats was monitored by flow cytometry, that of young rats was taken as control. （2） The differential expression profile of NF-κB related signals in aged rats allocated in the control group （aged rats, group A）, the EF treated group （group B）, the PDTC （a NF-κB inhibitor） treated group （group C） and the PDTC plus EF treated group （group D）, was determined and the main significant molecules in them were analyzed with gene microarray of 96 genes related to NF-κB signal pathway. Results Excessive apoptosis of T lymphocyte cell was seen in aged rats, and it was significantly suppressed in group B and D. In group B, 73 genes were up-regulated to different extent, including 10 of the NF-κB/Rel/IB gene family, transduction signal molecule member of N IK/IKK/I B/Rel/NF-κB, NF-κB regulatory target genes, trans-membrane receptors, transcription factors, and receptor protein, etc. But the up-regulation on NF-κB gene family could not be seen in group C and that on others were also alleviated, while in the group D, the NF-κB gene family and its related transduction pathway were still activated to some extent. The NF-κB gene family showed a markedly common feature after EF intervention, either used alone or in combination with PDTC, i.e. the significant upregulated NF-κB1, NF-κB2, Rel B and I Bε, and activated NIK/IKK/I B/Rel/NF-κB pathway.Conclusion EF can suppress the excessive apoptosis of splenic lymphocyte in aged rats and activate Rel/NF-κB/ I B/IKK and their signal transduction pathway to up-regulate NF-κB through adjusting I Bε and I Bα, which may be the essential mechanism of EF in rebuilding the immune homeostasis of T lymphocyte apoptosis and retarding immunosenescence.
出处
《中国中西医结合杂志》
CAS
CSCD
北大核心
2006年第7期620-624,共5页
Chinese Journal of Integrated Traditional and Western Medicine
基金
国家自然科学基金(No.30500681)
中国博士后基金(No.2004036339)
