淫羊藿总黄酮通过抑制MAPK/NF-κB信号通路减轻自然衰老大鼠脑组织炎症反应  

Total flavonoids of Epimedium attenuate aging-related inflammation in rat brain by inhibiting MAPK/NF-κB signaling pathway

作　　者：宋来新[1] 张长城[1] 王婷[1] 刘珍财 韩贵芳 袁丁[1,2] 赵海霞[1] 

机构地区：[1]三峡大学医学院国家中医药(肿瘤)管理局三级实验室,湖北宜昌443002 [2]三峡大学仁和医院,湖北宜昌443002

出　　处：《中国药理学通报》2017年第1期84-90,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81373881;81374001;81503334);三峡大学人才科研启动基金项目(No KJ2014B067)

摘　　要：目的探讨淫羊藿总黄酮(total flavonoids of Epimedium,TFE)对自然衰老大鼠脑组织中MAPK/NF-κB信号通路影响及其抗炎作用。方法 HE染色观察各组大鼠海马CA1、CA3和DG区神经元形态的变化。Western blot法检测各组大鼠海马组织中衰老相关蛋白p21、凋亡相关蛋白Bax和Bcl-2的表达,核转录因子NF-κB p65及其下游炎症因子TNF-α、IL-1β和COX-2的表达,以及MAPK信号通路相关蛋白的表达。结果 TFE可明显改善自然衰老组大鼠海马神经细胞形态结构,神经细胞排列整齐紧密。同时,TFE可明显下调自然衰老组大鼠海马组织中p21、Bax蛋白表达水平,上调Bcl-2蛋白表达水平及Bcl-2/Bax的比值,且可明显降低NF-κB p65核蛋白及其下游炎症因子TNF-α、IL-1β和COX-2的表达,以及MAPK信号通路相关蛋白(p-ERK1/2、p-JNK、p-p38 MAPK)的表达。结论 TFE对自然衰老大鼠炎症反应具有保护作用,其作用机制可能是通过抑制MAPK信号通路的激活,从而抑制NF-κB的核易位及其下游炎症细胞因子表达,进而延缓脑衰老。Aim To investigate the effect of the total flavonoids of Epimedium（ TFE） on MAPK / NF-κB signaling pathway and the inflammatory reaction in the hippocampus of natural aging male rats. Methods The morphological changes of the hippocampus composed of three areas（ CA1,CA3 and DG） were ob-served using haematoxylin-eoin（ HE） staining. The protein expression levels of senescence-associated protein p21,apoptosis-related proteins Bax and Bcl-2,nuclear transcription factor-κB p65（ NF-κB p65） and its downstream inflammatory factors TNF-α,IL-1β and COX-2,and MAPK signaling pathway-related proteins（ ERK1 /2,p-ERK1 /2,JNK,p-JNK,p38 MAPK,pp38MAPK） in hippocampal were detected by Western blot. Results Compared with natural aging group,TFE obviously improved the morphology and structure of hippocampal neurons,and the nerve cells arranged neatly and closely. Furthermore, TFE significantly downregulated the protein expression levels of p21 and Bax,upregulated the protein expression levels of Bcl-2and the ratio of Bcl-2 / Bax,and reduced the expression of NF-κB p65 and of its downstream inflammatory factors TNF-α, IL-1β, COX-2, and MAPK signalingpathway-related proteins（ p-ERK1 /2,p-JNK and pp38 MAPK） in hippocampus of natural aging rats.Conclusions TFE effectively protects against inflammatory reaction in brain aging of SD male rats. The mechanism is related with inhibition of NF-κB nuclear translocation and reduction of its downstream inflammatory cytokines expression by inhibiting MAPK signaling pathway activation.

关 键 词：淫羊藿总黄酮 衰老 海马 炎症 P21 MAPK NF-ΚB 

分 类 号：R-332[医药卫生] R284.1