世界科学技术-中医药现代化2025，Vol.27Issue(3)：724-738,15.DOI:10.11842/wst.20240422006
六味地黄丸通过FcγRⅡB/c-Src通路干预自噬防治阿尔茨海默病的分子机制
Liuwei Dihuangwan lnterferes with the Molecular Mechanism of Autophagy Prevention and Treatment of Alzheimer's Disease through FcγRⅡB/c-Src Pathway
摘要
Abstract
Objective To study the effect of Liuwei Dihuangwan on autophagy level and its mechanism in SAMP8 mice and Aβ-stimulated BV2 cell model,and to explore the molecular mechanism of tonifying the kidney and filling up the essence to prevent and control Alzheimer's disease(AD)through interfering with autophagy.Methods Ten 7-month-old male anti-aging mice(SAMR1)were taken as the normal group,and 40 7-month-old male rapid aging mice(SAMP8)were randomly control and model groups,equal volumes of saline were administered by gavage twice a day for 4 weeks,and the levels of Aβ expression in the hippocampus of the mice in each group were detected by immunofluorescence;The expression levels of FcγRⅡB,c-Src and SHP-1 in the hippocampus of each group were detected by Western blot;BV2 cells were cultured and Fcγ receptor Ⅱ-b(FcγRⅡB)overexpression vectors were constructed;the AD state cell model was established by treating the BV2 cells with 5 µmol·L-1 Aβ1-42,and the Liuwei Dihuangwan drug-containing serum was prepared.The cells were divided into NC group,Aβ1-42 group,blank serum group,drug-containing serum group,Vector group,FcγRⅡB OE group,and drug-containing serum+FcγRⅡB OE group;immunofluorescence was used to detect the expression level of Aβ protein in the cells of each group;Western blot was used to detect the expression level of p62,LC3 Ⅱ/Ⅰ,FcγRⅡB,SHP-1,and c-Src in cells of each group.Results Compared with the normal group,the hippocampal Aβ,FcγRⅡB,SHP-1,and c-Src expression levels in the model group of mice were significantly higher(P<0.01),and compared with the model group,the expression levels of Aβ,FcγRⅡB,SHP-1,and c-Src in the low-,medium-,and high-dose groups of Liuwei Dihuangwan were significantly lower(P<0.01),it also showed a significant dose dependent relationship.Compared with NC group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in Aβ1-42 group were significantly increased(P<0.01),and LC3Ⅱ/Ⅰ was significantly decreased(P<0.01);Compared with Aβ1-42 group and blank serum group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in drug-containing serum group were significantly decreased(P<0.01),and LC3Ⅱ/Ⅰ was significantly increased(P<0.01);Compared with NC group and Vector group,the expression of Aβ in FcγRⅡB OE group was increased,the protein expressions of p62,FcγRⅡB,SHP-1 and c-Src were significantly increased(P<0.01),and LC3Ⅱ/Ⅰ was significantly decreased(P<0.01);Compared with the drug-containing serum group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in the drug-containing serum+FcγRⅡB OE group were significantly increased(P<0.01),and the protein expression levels of LC3Ⅱ/Ⅰ were significantly decreased(P<0.01).Conclusion Liuwei Dihuangwan improved AD by inhibiting microglia FcγRⅡB/c-Src pathway and increasing autophagy level.关键词
阿尔茨海默病/六味地黄丸/FcγRⅡB/c-Src/自噬Key words
Alzheimer's disease/Liuwei Dihuangwan/FcγRⅡB/c-Src/Autophagy分类
医药卫生引用本文复制引用
侯文晓,司蕊豪,刘羽茜,朱仲康,殷正达,王旭,赵丹玉..六味地黄丸通过FcγRⅡB/c-Src通路干预自噬防治阿尔茨海默病的分子机制[J].世界科学技术-中医药现代化,2025,27(3):724-738,15.基金项目
国家自然科学基金委员会面上项目(82374166):基于"肾通于脑"理论探讨补肾填精法调控GPNMB介导的自噬缓解小胶质细胞免疫衰老重塑微环境防治AD的分子机制,负责人:赵丹玉 （82374166）
辽宁省教育厅基本科研项目面上项目(LJKMZ20221317):补肾填精法调控阿尔茨海默病脑免疫微环境重塑的分子机制研究,负责人:赵丹玉. （LJKMZ20221317）
