Qijia Rougan Decoction Ameliorates Liver Fibrosis Through miRNA-mRNA Network
10.13422/j.cnki.syfjx.20251901
- VernacularTitle:芪甲柔肝方通过miRNA-mRNA网络改善肝纤维化的作用机制
- Author:
Yumei WANG
1
;
Peijie WU
1
;
Shaoxiu JI
2
;
Han YU
1
;
Xiaohong ZUO
3
;
Xiaofeng CHEN
1
Author Information
1. School of Basic Medical Sciences， Chengdu University of Traditional Chinese Medicine（TCM）， Chengdu 611137， China
2. Yinchuan Hospital of TCM， Yinchuan 750001， China
3. Ineye Hospital of Chengdu University of TCM，Chengdu 610084， China
- Publication Type:Journal Article
- Keywords:
Qijia Rougan decoction;
liver fibrosis;
miRNA-mRNA regulatory network;
metabolic reprogramming;
phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(14):84-90
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanism by which Qijia Rougan decoction ameliorates liver fibrosis through amino acid/fatty acid metabolic reprogramming and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway， based on the miRNA-mRNA regulatory network and the interaction between metabolism and signaling pathways. MethodsSprague-Dawley （SD） rats were randomized into four groups （n=8）： control， model， and low-dose and high-dose （7.0， 28.0 g·kg-1·d-1， respectively） Qijia Rougan decoction. Liver fibrosis was induced by subcutaneous injection of carbon tetrachloride （CCl4）. From week 9， drug intervention was implemented for 7 weeks. After the final administration， the pathological changes in the liver were evaluated through hematoxylin-eosin （HE） and picrosirius red （PSR） staining. An automated biochemical analyzer was used to measure the serum levels of biochemical indicators， including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， alkaline phosphatase （ALP）， total bile acid （TBA）， albumin （ALB）， and cholesterol （TC）. High-throughput miRNA sequencing was performed to identify differentially expressed miRNAs （DemiRs） during liver fibrosis. A miRNA-mRNA interaction network was constructed to identify key targets， which were then subjected to GO and KEGG enrichment analyses. The expression levels of selected DemiRs were validated by Real-time PCR. ResultsCompared with the control group， the model group showed marked hepatic lobular necrosis， increased collagen deposition， significant fibrosis， elevated serum levels of ALT， AST， ALP， and TBA （P<0.01）， and declined levels of ALB and TC （P<0.01）. Compared with the model group， Qijia Rougan decoction treatment reduced hepatic necrosis， collagen accumulation， and fibrosis， lowered the serum levels of ALT， AST， ALP， and TBA （P<0.01）， and raised the levels of ALB and TC （P<0.01）. Integrated miRNA-seq and RNA-seq analysis identified 31 DemiRs （6 upregulated and 25 downregulated） and 498 targets. The expression trends of four selected DemiRs， including rno-miRNA-376b-3p， were consistent with sequencing results （R2=0.93）. Functional annotation revealed that top 20 upregulated targets were enriched in amino acid and fatty acid metabolism， while top 20 downregulated targets were significantly associated with the PI3K/Akt signaling pathway and cancer progression. ConclusionQijia Rougan decoction alleviates liver fibrosis by reconstructing the miRNA-mRNA regulatory network， promoting metabolic reprogramming， and inhibiting the PI3K/Akt signaling pathway. These findings provide mechanism evidence supporting the multi-targeted antifibrotic effects of traditional Chinese medicine compound formulas.
