Yiqi-Yangyin-Quyu prescription attenuates skeletal muscle injury and related metabolic disorders in mice with Sj?gren syndrome by targeting Hadhb
10.3969/j.issn.1000-4718.2025.09.015
- VernacularTitle:益气养阴祛瘀方通过促进Hadhb表达减轻干燥综合征小鼠骨骼肌损伤及相关代谢紊乱
- Author:
Ting ZHAO
1
;
Yue SHEN
1
;
Wenyue JIAO
1
;
Xinyi YAO
1
;
Dingqi LU
1
;
Yating REN
1
;
Liying CHEN
1
;
Yihan WANG
1
;
Wenhan HUANG
1
;
Runrun ZHANG
1
;
Xinchang WANG
1
Author Information
1. 浙江中医药大学第二临床医学院,浙江 杭州 310005
- Publication Type:Journal Article
- Keywords:
Yiqi-Yangyin-Quyu prescription;
Sj?gren syndrome;
skeletal muscle injury;
transcriptome;
proteome
- From:
Chinese Journal of Pathophysiology
2025;41(9):1793-1806
- CountryChina
- Language:Chinese
-
Abstract:
AIM:The aim of this study was to explore the effects of Yiqi-Yangyin-Quyu prescription(YP)on skeletal muscle injury and related metabolic disorders in mice with Sj?gren syndrome(SS),and to clarify the role of hy-droxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta(Hadhb)in mediating the effect of YP on skeletal muscle in SS.METHODS:The SS mice underwent YP treatment for 8 weeks.The morphological changes of the submandibular gland and muscle tissue were examined using hematoxylin-eosin staining.The mitochondrial status in mus-cle tissue was assessed through transmission electron microscopy.Additionally,combined transcriptome and proteome se-quencing was conducted on skeletal muscle samples.The omics sequencing results were validated by RT-qPCR.Immuno-fluorescence was used to confirm the levels of key proteins involved in the P53/peroxisome proliferator-activated receptor gamma(PPARG)signaling pathway.Immunohistochemistry and Western blot were employed to determine the levels of Hadhb key targets.RESULTS:Combined transcriptome and proteome analysis identified 1 523 differentially expressed genes(DEGs)and 182 differentially expressed proteins(DEPs)between the muscle tissue of SS mice(model group)and that of control animals(ICR group),12 of which showed co-differential expression at both transcriptomic and proteomic levels.Compared with model group,1 232 genes and 432 proteins were found to be differentially expressed in the muscle tissue of the mice in YP group.Among these,23 exhibited co-differential expression at both mRNA and protein levels.Gene Ontology(GO)analysis showed that the DEGs and DEPs between ICR and model groups were mainly involved in ener-gy metabolism and fatty acid oxidation,while the DEGs and DEPs between YP and model groups were primarily associated with sarcomere tissue and actin structure.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis indi-cated that the DEGs and DEPs between ICR and model groups and between model and YP groups were enriched in the com-plement and coagulation cascade and lipid and pyruvate metabolism.The RT-qPCR validation results were consistent with those of the transcriptome analysis.Furthermore,the protein expression of the tumor suppressor P53 was significantly de-creased in YP group compared with model group,whereas that of PPARG was significantly increased.Western blot analy-sis showed that compared with ICR group,Hadhb protein expression was significantly decreased in model group,whereas the opposite trend was detected in YP group.CONCLUSION:The SS-related skeletal muscle damage is closely related to amino acid metabolism disorder and fatty acid degradation.Treatment with YP modulates innate immune defenses,lipid metabolism and energy metabolism in SS,and Hadhb is the key target of YP in SS-related skeletal muscle.
