从AMPK-mTOR信号途径研究淫羊藿总黄酮对衰老大鼠皮层自噬的调节作用  

Regulatory effect of total flavonoids of epimedium on autophagy in cerebral cortex of natural aging rats via AMPK-mTOR signaling pathway

作　　者：张续蓝 王婷 郑杰 望金欣 袁丁[1] 张长城[1] 周志勇[1] ZHANG Xu-lan;WANG Ting;ZHENG Jie;WANG Jin-xin;YUAN Ding;ZHANG Chang-cheng;ZHOU Zhi-yong(College of Medical Science, China Three Gorges University, Yichang Hubei 443002, China;College of Medical Science, Wuhan University of Science and Technology, Wuhan 430081, China)

机构地区：[1]三峡大学医学院,湖北宜昌443002 [2]武汉科技大学医学院,湖北武汉430081

出　　处：《中国药理学通报》2020年第10期1445-1449,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81673778)。

摘　　要：目的探讨淫羊藿总黄酮(total flavonoids of epimedium,TFE)对自然衰老大鼠皮层自噬的调节作用及分子机制。方法HE染色和Nissl染色观察大鼠皮层神经元形态学变化,Western blot检测自噬相关蛋白LC3、p62、Beclin1以及AMPK-mTOR信号途径关键蛋白在皮层组织中的表达水平。结果HE染色和Nissl染色结果显示,与青年对照组大鼠相比,衰老模型组大鼠皮层神经元丢失,排列散乱,且变性神经元数量增多,给予淫羊藿总黄酮干预后,神经元数量增多,变性神经元数量减少;Western blot结果表明,与青年大鼠相比,自然衰老大鼠下调p-AMPK/AMPK、LC3Ⅱ/Ⅰ、Beclin1蛋白表达水平,上调p-mTOR/mTOR、p62蛋白表达水平,给予淫羊藿总黄酮干预后可上调p-AMPK/AMPK、LC3Ⅱ/Ⅰ、Beclin1蛋白表达水平,下调p-mTOR/mTOR、p62蛋白表达水平。结论TFE可上调自然衰老大鼠皮层自噬,其机制可能与调节AMPK-mTOR信号途径有关。Aim To study the regulatory effect of total flavonoids of epimedium(TFE)on autophagy in cere-bral cortex of natural aging rats and explore the potential mechanism.Methods The cortex morphology was observed using HE staining and Nissl staining.The expression levels of related proteins of autophagyincluding LC3,p62,Beclin1 and key proteins of AMPK-mTOR signaling pathway were detected by Western blot.Results HE staining and Nissl staining showed that the number of neurons in the aging model group decreased with the scattered arrangement and the denatured feature.However,TFE treatment improved the neuronal pathomorphology and decreased the number of denatured neurons in cerebral cortex of natural aging rats.Western blot results demonstrated that the protein expression levels of p-AMPK/AMPK,LC3Ⅱ/Ⅰ,Beclin1 decreased,while the levels of p-mTOR/mTOR,p62 increased in aging model group in comparison with the adult control group.And TFE treatment could increase the levels of p-AMPK/AMPK,LC3Ⅱ/I,Beclin1,whereas decreased the levels of p-mTOR/mTOR and p62.Conclusions TFE activates autophagy in cerebral cortex of natural aging rats through regulation of the AMPK-mTOR signaling pathway.

关 键 词：淫羊藿总黄酮 衰老 大鼠 皮层 自噬 AMPK-mTOR信号途径 

分 类 号：R-332[医药卫生] R284.1