时珍国医国药2025，Vol.36Issue(19)：3639-3645,7.DOI:10.70976/j.1008-0805.SZGYGY-2025-1906
基于ULK1/FUNDC1通路探讨补中益气汤调控线粒体自噬防治肌少症的机制研究
To explore the mechanism of Buzhong Yiqi Decoction(补中益气汤)in regulating mitochon-drial autophagy in the prevention and treatment of sarcopenia based on the ULK1/FUNDC1 pathway
摘要
Abstract
Objective To investigate the role of Buzhong Yiqi Decoction(补中益气汤,BZYQD)in preventing and treating sarcopenia by regulating the ULK1/FUNDC1 pathway and influencing mitochondrial autophagy.Methods SD rats were randomly divided into the blank control group(KB group),the model group(MX group),and the BZYQD group.Sarcopenia models were established in the MX and BZYQD groups using the tail suspension method.Drugs were administered during modeling.After 8 weeks,the muscle strength of the forelimbs and hindlimbs was measured.Subsequently,aortic serum and bilateral gastrocnemius muscles of rats in each group were collected.The gastrocnemius muscle is used for the determination of mass and gastrocnemius musde index.The MyoG protein content in serum and GAS muscle tissue was measured by ELISA,and MyoD mRNA expression in the GAS muscle was quantified by RT-qPCR.Pathological changes in the GAS muscle were observed using HE and Masson staining.LC3 protein expression in the GAS muscle was detected by immunohistochemistry(IHC).The levels of ROS,MDA,SOD,and GSH-Px,as well as the ATP content,in the GAS muscle were measured using ELISA,WST-1,TBA,and colorimetric assays,respectively.The protein expression levels of PGC-1α,Beclin-1,UCP2,p62,p-ULK1(Ser555)/ULK1,p-FUNDC1(Ser17)/FUNDC1,and LC3-Ⅱ/LC3-Ⅰ in the GAS muscle were deter-mined by Western blot(WB).Results Compared with the KB group,rats in the MX group showed decreased GAS muscle mass and index,reduced muscle strength of the forelimbs and hindlimbs,lower MyoG protein content,and diminished MyoD mRNA expression.Additionally,levels of ROS and MDA were elevated,while levels of SOD and GSH-Px,as well as ATP content,were reduced.The expression levels of PGC-1α,UCP2,p62,the p-ULK1(Ser555)/ULK1 ratio,the p-FUNDC1(Ser17)/FUNDC1 ratio,and the LC3-Ⅱ/LC3-Ⅰ ratio were all decreased.Moreover,pathological examination of the GAS muscle revealed significant atrophy,reduced myofiber cross-sectional area,and increased interstitial space with sparse cellularity.Collagen fiber proliferation and deposition were increased.Compared with the MX group,the BZYQD group showed significant improvements in all the aforementioned parameters and also pro-moted the expression of proteins associated with the ULK1/FUNDC1 signaling pathway.Conclusion BZYQD reduces oxidative stress and alleviates mitochondrial function through ULK1/FUNDC1 pathway-mediated mitochondrial autophagy,thereby playing a role in the prevention and treatment of sarcopenia.关键词
肌少症/补中益气汤/线粒体自噬/Unc-51样自噬激活酶1/FUN14域含蛋白1Key words
Sarcopenia/Buzhong Yiqi Decoction(补中益气汤)/Mitochondrial autophagy/ULK1/FUNDC1分类
医药卫生引用本文复制引用
付夜平,杨芳,胡楠,孙鑫,杨蓝鑫,方佳琪..基于ULK1/FUNDC1通路探讨补中益气汤调控线粒体自噬防治肌少症的机制研究[J].时珍国医国药,2025,36(19):3639-3645,7.基金项目
国家自然科学基金(82104709) （82104709）
辽宁省应用基础研究计划(2022JH2/101300105) （2022JH2/101300105）
辽宁省应用基础研究项目(2023JH2/101700241) （2023JH2/101700241）
辽宁省教育厅项目(2024-JYTCB-009) （2024-JYTCB-009）
