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已发表论文
口服丹参来源细胞外囊泡对糖尿病肾病的保护作用：由肠道微生物群和代谢组重塑介导的保护
Authors Liu Y, Feng Z, Huang J, He J , Li L, Yu R
Received 26 November 2025
Accepted for publication 1 February 2026
Published 13 February 2026 Volume 2026:21 580968
DOI https://doi.org/10.2147/IJN.S580968
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr RDK Misra
Yi Liu,1,* Zhiying Feng,1,* Jiawang Huang,1 Jiacheng He,2 Liu Li,1 Rong Yu1
1College of Traditional Chinese Medicine of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 2College of Integrated Traditional Chinese and Western Medicine of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Rong Yu, College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Xueshi Road 300, Changsha, Hunan, 410208, People’s Republic of China, Email yurong196905@163.com Jiawang Huang, College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Xueshi Road 300, Changsha, Hunan, 410208, People’s Republic of China, Email 1518522909@qq.com
Purpose: Diabetic kidney disease (DKD) is one of the most common and severe microvascular complications of diabetes, characterized by glomerulosclerosis and tubulointerstitial fibrosis. Growing evidence indicates that gut dysbiosis and metabolic imbalance contribute to DKD progression. Salvia miltiorrhiza possesses anti-inflammatory, antioxidative, and antifibrotic activities, while Salvia miltiorrhiza‐derived Extracellular Vesicle (SMEVs), as natural nano-carriers, exhibit favorable bioactivity and targeting potential.
Methods: SMEVs were isolated and purified using differential centrifugation combined with sucrose density gradient ultracentrifugation. Transmission electron microscopy and nanoparticle tracking analysis confirmed their typical bilayer membrane and an average diameter of approximately 163.6 nm. BKS.DB mice were orally administered SMEVs for 6 weeks, followed by evaluation of renal function, histopathology, and molecular markers.
Results: SMEV treatment significantly improved glucose and lipid metabolism, reduced proteinuria, alleviated renal dysfunction, and mitigated renal fibrosis in DKD mice. 16S rRNA sequencing revealed that SMEVs reshaped the gut microbial community by increasing beneficial taxa and suppressing pathogenic bacteria. Untargeted metabolomics demonstrated that SMEVs reversed DKD-associated metabolic disturbances, characterized by the upregulation of bioactive peptides (eg, Tyr-Leu-His) and unsaturated fatty acids (eg, petroselinic acid), along with the reduction of pro-inflammatory lipids. KEGG enrichment indicated significant modulation of arachidonic acid, linoleic acid, and amino acid metabolism pathways. Spearman correlation analysis further revealed strong associations between key microbial taxa and differential metabolites, suggesting coordinated regulation of gut microbiota and metabolism during SMEV-mediated protection.
Conclusion: SMEVs significantly improve the pathological progression of DKD by reshaping the intestinal flora, restoring metabolic homeostasis and inhibiting inflammatory and fibrotic responses, providing an experimental basis for the application of plant-derived extracellular vesicles in kidney diseases.
Keywords: diabetic kidney disease, gut microbiota, Salvia miltiorrhiza–derived extracellular vesicles, extracellular vesicles, metabolomics
1College of Traditional Chinese Medicine of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 2College of Integrated Traditional Chinese and Western Medicine of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Rong Yu, College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Xueshi Road 300, Changsha, Hunan, 410208, People’s Republic of China, Email yurong196905@163.com Jiawang Huang, College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Xueshi Road 300, Changsha, Hunan, 410208, People’s Republic of China, Email 1518522909@qq.com
Purpose: Diabetic kidney disease (DKD) is one of the most common and severe microvascular complications of diabetes, characterized by glomerulosclerosis and tubulointerstitial fibrosis. Growing evidence indicates that gut dysbiosis and metabolic imbalance contribute to DKD progression. Salvia miltiorrhiza possesses anti-inflammatory, antioxidative, and antifibrotic activities, while Salvia miltiorrhiza‐derived Extracellular Vesicle (SMEVs), as natural nano-carriers, exhibit favorable bioactivity and targeting potential.
Methods: SMEVs were isolated and purified using differential centrifugation combined with sucrose density gradient ultracentrifugation. Transmission electron microscopy and nanoparticle tracking analysis confirmed their typical bilayer membrane and an average diameter of approximately 163.6 nm. BKS.DB mice were orally administered SMEVs for 6 weeks, followed by evaluation of renal function, histopathology, and molecular markers.
Results: SMEV treatment significantly improved glucose and lipid metabolism, reduced proteinuria, alleviated renal dysfunction, and mitigated renal fibrosis in DKD mice. 16S rRNA sequencing revealed that SMEVs reshaped the gut microbial community by increasing beneficial taxa and suppressing pathogenic bacteria. Untargeted metabolomics demonstrated that SMEVs reversed DKD-associated metabolic disturbances, characterized by the upregulation of bioactive peptides (eg, Tyr-Leu-His) and unsaturated fatty acids (eg, petroselinic acid), along with the reduction of pro-inflammatory lipids. KEGG enrichment indicated significant modulation of arachidonic acid, linoleic acid, and amino acid metabolism pathways. Spearman correlation analysis further revealed strong associations between key microbial taxa and differential metabolites, suggesting coordinated regulation of gut microbiota and metabolism during SMEV-mediated protection.
Conclusion: SMEVs significantly improve the pathological progression of DKD by reshaping the intestinal flora, restoring metabolic homeostasis and inhibiting inflammatory and fibrotic responses, providing an experimental basis for the application of plant-derived extracellular vesicles in kidney diseases.
Keywords: diabetic kidney disease, gut microbiota, Salvia miltiorrhiza–derived extracellular vesicles, extracellular vesicles, metabolomics